Charles TRUILLET
BioMaps – U1281 – CEA – Université Paris Saclay – ORSAY
Gaëtane NOCTURNE
UMR-S 1184 IMVA – Hôpital de Bicêtre – KREMLIN-BICETRE
Sjögren’s disease (Sjo) is an autoimmune disease characterised by lymphocyte infiltration, leading to a dry syndrome. In 30% of patients, it leads to systemic involvement. Unfortunately, there is currently no validated treatment for Sjo’s disease. The disease is characterised by chronic activation of B lymphocytes, based on complex communication between epithelial cells, particularly those of the salivary glands (SGEC), and immune cells. It is crucial to develop preclinical models of the disease that integrate the epithelial cells and the immune compartment.
The advent of patient-derived organoids has revolutionised preclinical models in cancer. Organoids model the interactions between patient tissue and immune cells. These models make it possible to accurately predict the body’s response to immunotherapies, including side effects. They therefore represent a significant step towards personalised medicine in cancer treatment.
Our teams are working to develop immuno-organoids derived from patients’ salivary glands as new study models for Sjögren’s disease and as a screening platform for potential therapies. This project is at the interface between autoimmunity and cancer. We aim to optimise patient-derived organoids developed in the context of cancer and apply them to the field of autoimmunity. In turn, we will use these organoids to gain a better understanding of the side effects associated with immunotherapy.
David MICHONNEAU
Service d’Hématologie – Hopital Saint Louis – PARIS
Acquired Aplastic Anemia (AAA) is characterized by a bone marrow failure secondary to an abnormal T-cell immune response against hematopoietic stem cells, with treatment relying on the use of immunosuppressive drugs or allogeneic hematopoietic stem cell transplantation. One of the most severe complications is progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), affecting over 20% of patients. Upon diagnosis, nearly 30% of patients already present somatic mutations within hematopoietic stem cells (HSCs), and the risk of clonal evolution persists in patients treated with immunosuppressive drugs who have achieved complete response. The abnormally high frequency of these mutations, even in young patients, suggests they may also play a role in initiating an abnormal immune response against the hematopoietic stem cell. The objective of this study is to characterize the biological mechanisms contributing to the clonal evolution of AAA patients, and potentially identify new therapeutic targets. This project relies on the use of bone marrow samples from AAA patients, at diagnosis and during follow-up after immunosuppressive treatments. We will combine comprehensive mapping of immune cells and their transcriptomic profile with a study of clonal mutations of HSC, and their consequences on the transcriptomic profile and functional properties of HSCs. This work will enable us to better understand the relationship between HSC mutations and the abnormal immune response directed against these cells, and to identify the mechanisms leading to progression to malignant hematopathy.
Marianne BURBAGE
U932 Immunité et Cancer – Institut Curie -PARIS
Defining what makes cancer cells visible for the immune system is a key question to improve immunotherapeutic protocols. The immune system can detect fragments of intracellular proteins (called antigens) that are exposed on cell membranes. Specialized immune cells, called T lymphocytes, recognize such motifs at the cell surface and react only to those they identify as “abnormal”.
Classically, scientists have focused on antigens deriving from mutations that tumor cells accumulate. However, we have recently learnt that in cancer cells, some T lymphocytes recognize antigens that derive from regions of the genome that are not typically expressed (“dark”) but that “awaken” during oncogenesis. While they are promising target, “dark” antigens are poorly defined from an immunological perspective. It is for example critical to determine to what extent “dark” antigens are considered part of the immune “self”. Indeed, the immune system is “educated” to prevent recognition of “normal” antigens that could result in auto-immunity. This education takes place in an organ called thymus. The project we proposed aims at defining the expression of “dark” antigens in the thymic cells that educate the immune system. The data generated in this project will constitute a useful resource for the scientific community and will be instrumental to instruct the selection of targets to improve immunotherapies and anti-tumor vaccination.
Olivier BERNARD
INSERM U1170 – Gustave Roussy – VILLEJUIF
Our immune system is made up of different cell types, including B cells, which play a crucial role in adaptive immunity. These atypical CD11c+ B cells (ABCs) are linked to immune responses triggered by vaccinations, infections and autoimmune diseases, in both mice and humans. Recent studies indicate that they are a step towards the development of lymphomas such as Waldenström’s macroglobulinemia (WM). Through analysis of models and patient samples, we will identify the intrinsic and extrinsic mechanisms that lead to the progression and aggressiveness of WM, and their relations with ABCs.
Eric TARTOUR
INSERM U970 – Centre de recherche PARCC (HEGP) – PARIS
Immunotherapy (IO) is based on the stimulation of immune cells against cancer. There are situations where these immune cells are resistant to this activation. In this project, we aim to validate a new resistance mechanism based on an interaction between the CD70 molecule expressed by tumor cells and the CD27 molecule present on certain immune cells. In addition, the CD27 molecule can be measured in plasma (sCD27). High sCD27 values may predict resistance to some forms of IO but not others in kidney cancer and melanoma patients. We will evaluate in this study the role of sCD27 biomarker in different types of current IO treatment to better guide and personalize possible therapeutic options in kidney cancer and melanoma patients.
Sophie LOTERSZTAJN
UMR 1149 – Université Paris Cité Faculté de Médecine – Site Bichat – PARIS
Chronic liver diseases are marked by a high burden due to the occurrence of fibrosis its end-stage cirrhosis, and hepatocellular carcinoma (HCC). They constitute a major public health problem with high mortality, 2/3 of which is linked to liver cancer, which makes cirrhosis a precancerous condition. Chronic inflammation plays a major role in the progression of the disease and constitutes a privileged target for reducing fibrosis and preventing cancer. Clonal hematopoiesis or “CHIP” is the presence of one or more mutations in blood cells, which can lead to hematological cancer and expose one to an increased risk of chronic inflammatory diseases. Our project aims to establish the relationship between CHIP, cirrhosis and progression to liver cancer, as well as to define the common mechanisms involved.
Christel GOUDOT
U932 Immunité et Cancer – Institut Curie -PARIS
In recent decades, cancer vaccines have raised hopes, as they have been able to stimulate immune response against tumor antigens. Nevertheless, immunosuppression is major challenge. It is therefore essential to improve and broaden the repertoire of antigens for vaccines. Recently, new classes of tumor antigens have been discovered, such as transposable elements, as a broad source of tumor neo-peptides. Nevertheless, the immunogenicity of the latter remains an important issue to be addressed. We therefore propose to combine state-of-the-art artificial intelligence methods with experimental validation to characterize immunogenic peptides derived from these regions. This will open up promising new therapeutic perspectives in cancer immunotherapy.
Franck CARBONNEL
Service de Gastroentérologie – Hôpital Bicêtre -KREMLIN-BICÊTRE
Immune checkpoint inhibitors (ICI) are a major advance in the treatment of cancer. They facilitate the elimination of cancer cells by stimulating immune cells. Yet, the therapeutic effect of ICI is variable, even in patients with tumors sensitive to ICIs (melanoma, lung cancer, urinary tract cancer). The composition of the intestinal microbiota is associated with the efficacy and safety of ICI. ATHENA aims to describe the microbiota metabolites associated with response and toxicity of ICIs, and to understand their interaction with immunity within the tumor. This study extends 2 clinical studies completed by our group. The results will contribute to the development of probiotics, prebiotics and metabolites from gut bacteria, in order to improve the safety and efficacy of ICI.
François-Xavier DANLOS
INSERM CIC 1428 – Gustave Roussy – VILLEJUIF
This project aims to understand how specific genetic variations increase the risk of autoimmune side effects in patients undergoing cancer immunotherapy. We focus on a particular genetic variant, rs7164391, to uncover the precise biological
mechanisms that explain why certain patients develop these reactions. This research will enhance the safety and effectiveness of cancer treatments.
Benjamin CHAIGNE
INSERM UMRS 1138 – Centre de Recherche des Cordeliers – PARIS
Systemic sclerosis (SSc) is a rare autoimmune disease characterized by vascular damage, fibrosis (tissue scarring), and inflammation. It is often linked with certain cancers, especially lung and breast cancer. Patients with SSc, particularly those with anti-RNA polymerase III antibodies, often show a clear connection between the onset of SSc and cancer, suggesting shared mechanisms. Fibroblasts play a central role in both SSc and cancer by producing excessive collagen in response to inflammatory signals. In SSc, this abnormal activation leads to progressive fibrosis, while in cancer, fibroblasts help create an environment that prevents immune cells from attacking the tumor. Additionally, the expression of inflammatory complement system proteins by fibroblasts has been linked to fibrosis. This project aims to understand the role of complement in fibroblasts, particularly in SSc associated with cancer. The research will focus on deciphering cancerassociated fibroblasts in SSc, analyze fibroblasts phenotypes and functions in response to -RNA polymerase III antibodies, and analyze complement-related fibroblast response in the lab. The goal is to clarify how fibroblasts contribute to the development of SSc associated cancer.
Raphaël JEGER-MADIOT
Autoimmunité et immunité lymphocytaire B – Institut Necker Enfants Malade – PARIS
In autoimmune diseases such as immune thrombocytopenia (IPT) and autoimmune hemolytic anemia (AIHA), the immune system mistakenly attacks the body’s platelets or red blood cells. Althrough the exact causes of these diseases are still poorly understood, the interaction between certain types of immune cells (B and t cells) in the spleen seems to be a key factor in this inappropriate response. However, studying this immune response in humans is difficult due to limited access to organs.
We propose to overcome this challenge by reproducing the tissue environment of the spleen using an organ-on-chip model, in order to mimic the immune dysfunction observed in patients. The goal will be to better understand how B and T cells react in our organ-on-chip model and wether we can reproduce the erroneous immune response against platelets and red blood cells observed in patients. Ultimately, our work could help determine whether certain forms of autoimmune cytopenias (responses against platelets and red blood cells) following cancer are the result of tumor T cells.
Jonathan POL
INSERM UMR 1138 – Centre de Recherche des Cordeliers – PARIS
Cholangiocarcinoma (CCA) is a rare but aggressive cancer of the bile ducts, often diagnosed at an advanced stage, limiting treatment options. Current therapies, including chemotherapy and immunotherapy, offer only partial effectiveness, highlighting the need for new approaches.
Our research explores the potential of therapeutic vaccines to stimulate the immune system against CCA. Inspired by immune mechanisms observed in certain liver diseases, we have identified tumor-specific antigens that could serve as vaccine targets. By developing an innovative vaccine strategy, we aim to enhance the body’s natural ability to recognize and fight CCA.
This project seeks to improve existing treatments and contribute to the development of personalized immunotherapies, offering new hope for patients affected by this challenging disease.
Samad MOHAMMADNEZHADDARYANI
INSERM UMR 981 – Gustave Roussy -VILLEJUIF
Immunotherapy helps the immune system fight cancer, but its effectiveness remains limited. T cells, which are responsible for attacking tumours, can become “exhausted”, losing their ability to fight cancer and no longer responding to treatments such as immune checkpoint inhibitors (ICIs). In addition, some patients suffer from serious side effects when their immune system attacks healthy tissue.
This project aims to improve immunotherapy by targeting messenger RNA translation, a key process in protein production. A complex called eIF4F plays a role in T cell exhaustion. By blocking one of its components, eIF4F, we hope to restore their activity, enhance the effectiveness of treatments and limit side effects. If this approach works, it could pave the way for new therapies that improve the effectiveness of immunotherapies while reducing their adverse effects.
Camille BIGENWALD
Immunologie des tumeurs et immunothérapie – Gustave Roussy – VILLEJUIF
CAR T cell therapy uses genetically modified T lymphocytes to target tumor cells. It is effective against B lymphomas, B leukemias and multiple myeloma resistant to more conventional treatments. Despite its efficacy, almost 40% of patients experience delayed hematological toxicity, persisting for more than 3 weeks after injection. This toxicity results in high morbidity, requiring transfusions and impacting quality of life. Initially attributed to the treatments previously administered to patients, we now know that it is linked to the injection of CAR T cells. The mechanism of this toxicity remains unknown, making its management non-standardized and necessitating in-depth study for its prevention and treatment.
Patricia LEPAGE
Micalis UMR 1319 – INRAE – JOUY-EN-JOSAS
Despite significant advances in cancer biology and crucial therapeutic innovations over the last decade, understanding individual trajectories in cancer treatment response remains an unreached goal. Metagenomics of the microbiome highlighted a link between our microbes, disease progression, and immunotherapy treatment response. While data-driven approaches have been developed to leverage the gut microbiome to ameliorate immunotherapy efficacy, the mechanisms underlying the interplay between the microbiome and treatment’s response are far from being resolved. The high inter-individual variability of the microbiome stands in the way of global therapeutic management. Yet, advances in microbial culturing technologies allow mimicking functional human-like microbiomes ex-vivo (microbiome avatars). Techniques such as fed-batch culturing reproduce nutritional and environmental conditions in bioreactors (also called anaerobic digesters or fermenters) and allow a longitudinal follow-up of microbial modifications/adaptations. The ambition of MelanoCult is to harness novel micro-fermentation technology (microfluidic-coupled micro-bioreactor) to develop personalized ex vivo microbiome avatars for patients with metastatic melanoma, in order to test and propose customized microbial modulation strategies to improve cancer response to immunotherapy.
Charles TRUILLET
BioMaps – U1281 – CEA – Université Paris Saclay – ORSAY
From targeted therapies to immunotherapies, including conjugated antibodies and vectorized radioimmunotherapies, antibodies play a pivotal role in cancer treatment, significantly extending patient survival and addressing aggressive cancers. However, only a subset of patients responds to these treatments, highlighting the need to identify predictive biomarkers for more precise patient selection and optimal treatment strategies. ImmunoPET medical imaging, which relies on the coupling of antibodies and radioisotopes, represents a significant advancement in patient care. A consortium from the University of Paris-Saclay leaded by the SHFJ is at the forefront of innovative research in ImmunoPET. A critical step in this project involves characterizing marked antibodies before and after radioligand injection using multidetector HPLC, UV, and radioactivity, forming the core of this funding proposal.
Françoise PORTEU
INSERM U1287 – Gustave Roussy – VILLEJUIF
Hematopoiesis is the physiological process by which all blood cells are produced. It resides mainly in the bone marrow, and begins with multipotent hematopoietic stem cells that differentiate into all hematopoietic lineages. During this differentiation, cells are characterized by a set of membrane markers known as cluster of differentiation. Hematopoiesis can be altered leading to myeloid or lymphoid hematological malignancies, which are the focus of INSERM U1287 and U1170. Our objectives are to understand their initiation and development, and to find curative treatments, notably by using multiparametric cytometry to assess the distribution of marrow and blood progenitors/precursors in normal and pathological contexts, before and after treatment, coupled with the cell cycle, activated signaling pathways and intracellular protein levels
Marie-Laure ARCANGELI
INSERM UMR1170 – Gustave Roussy – VILLEJUIF
Tumoral development is a multi-step process influenced by cell of origin of the oncogenic mutation as well as the way the different cancer cells respond to stress generated either by their microenvironment and/or therapies. Recent technics in genome manipulation and cell reprogramming (such as induced pluripotent stem cells, iPS) as well as the possibility to analyze single cells allow a better understanding in vitro of primary samples and the modeling of the transformation process. Therefore, the common approach of all the participants to this project is to design tumoral transformation models from primary cells, including ex-vivo analyses that will permit to better understand steps involved in oncogenesis and to set up functional screening for new therapeutical approaches. The realization of this project needs the acquisition of a performant microscope capable of automated analyses allowing for the analysis of multiple conditions.
Mehdi TOUAT
UMR S 1127 – Institut du Cerveau – PARIS
High-throughput imaging is a technique that enables automated optical microscopy and image analysis of large numbers of samples. Coupled with fluorescent markers, this technique allows the phenotypic analysis of cells of interest (e.g. tumor, immune) as well as the evaluation of their response to various perturbations (e.g. immunotherapy or genomic modification) in 2D cell culture or 3D organoid (in vitro cultures which show architecture and functions close to the ones of tissues from which they derive) models. Through this project, we will acquire a new microscope enabling high-throughput, high-resolution confocal microscopy imaging of live and fixed 2D cell cultures, tissues and organoid models. This will enable the detailed study of interactions between immune and tumor cells in new generation 3D models, the evaluation of new immunotherapy strategies, and the search for cellular or molecular mediators involved in dysimmune adverse reactions associated with cancer immunotherapies.
Samad MOHAMMADNEZHADDARYANI
INSERM U981 – Gustave Roussy – VILLEJUIF
This request is part of the MELAVATAR program, which aims to optimize the treatment of melanoma patients undergoing immunotherapy by developing algorithms that incorporate classical biomarkers obtained from tumor and blood samples of patients before and during treatment, as well as new markers developed in our laboratory, particularly concerning the metabolism of tumor and immune cells. These algorithms will be developed to address three main clinical objectives: 1) predicting the response to mono-immunotherapy with anti-PD1; 2) characterizing patients for whom treatment can be de-escalated (using a double immunotherapy injection instead of four); 3) predicting the occurrence of autoimmune-like side effects. The requested equipment will help optimize the isolation of relevant cell populations and quickly study their metabolic state ex-vivo.
Encarnita MARIOTTI-FERRANDIZ
UMRS959 – Immunologie – Immunopathologie – Immunothérapie – PARIS
Autoimmune and inflammatory disorders (AIDs) result from the body’s immune system attacking its own tissues and often arising as adverse events in cancer treatment with immune checkpoint inhibitors. There is a critical need for disease specific treatments and diagnostic markers. AIDs result from T and B lymphocytes losing self-tolerance to self-antigens. DeepAIRR proposes an innovative platform to explore AIDs through systems immunology approaches, focusing on single-cell and bulk sequencing of the T and B cell antigen specific receptors as well as their transcriptome. Leveraging the i3 lab expertise in AID research and omic data analysis, DeepAIRR aims to provide mechanistic insights into AID pathophysiology, potentially leading to new therapies and biomarkers, advancing patient care.
Julie HELFT
INSERM U1016, CNRS 8104 – Institut Cochin – PARIS
A simplified view of the tumor would be to think that this organ is composed of a cluster of cells that has accumulated genetic alterations leading to uncontrolled proliferation. However, it is now known that tumors are composed of a multitude of cell types within a complex microenvironment that promotes tumor growth and dissemination and influences the response to treatments. It is now possible to finely characterize the tumor microenvironment at the protein and transcriptomic level, thanks to new techniques of treatment of tumor tissue sections, in order to adapt immunotherapeutic treatments. The digitalization of these slides by a slide scanner is essential and will allow to analyze the complexity of the tumor microenvironment in a simple, fast and reproducible way.
Thomas MERCHER
INSERM U1170 – Gustave Roussy – VILLEJUIF
The genomic analyses carried out in recent years to characterize cancers have identifies genes that are mutated or whose expression is altered in tumor cells or in nearby cells like immune cells. In order to functionally validate these results and progress towards a clinical application of these observations, it is essential to quantify the expression and activation of the proteins encoded by these genes within the important cells of the tumors, which are often in limited supply for our analyses. In this project, we will use an equipment that requires a reduced number of cells to quantify protein expression and activation in different tumor
and immune cell subpopulations.
Cyril CATELAIN
INSERM UMR1170 – Gustave Roussy – VILLEJUIF
Understanding tumorigenesis processes requires the characterization of cells from patient samples. Flow cytometry is the most suitable technique because it allows a varied number of biological parameters to be examined. The CONCERTO project brings together 6 research teams on the Gustave Roussy site whose goal is to find new therapies for the benefit of the patient, either by characterizing all the cells collected during a biopsy (diseased cells and healthy cells), either by developing mouse models to assess the impact of “healthy” immune cells on the tumor, or by developing models to understand the process of cancerous transformation.
Aurélien MARABELLE
INSERM U1015 – CIC1428 – Gustave Roussy – VILLEJUIF
The PORTRAIT SPECTRAL project is dedicated to predicting and personalizing anti-tumor immunotherapies by analyzing fresh tissues (tumor biopsies and whole blood). The immunological portrait of each patient and their cancer is then used to guide these patients into appropriate therapeutic cohorts. The ITAC DIM has funded the acquisition of a technology that doubles the number of parameters analyzed on fresh tissues. This will allow for a more detailed analysis of the immunology of patients and their cancer, leading to the identification of new predictive biomarkers of efficacy and/or side effects and to propose new therapeutic options for patients with cancer.
Guy GOROCHOV
INSERM U1135 – CIMI-Paris – PARIS
Despite the progress in new anti-tumor immunotherapies that have dramatically improved the prognosis of many cancers, malignant brain tumors of the glioma type remain largely insensitive to these new approaches. Neither the treatments with antibodies capable of reactivating anti-tumor immunity, nor the new cellular therapies have been able to improve patient outcomes and their survival prognosis remains bleak. We will take advantage of rare situations where these brain tumors are infiltrated by B lymphocytes secreting antibodies of unknown specificity. We postulate that some of these antibodies will allow us to define the targets recognized in tumors. Moreover, such antibodies could be manufactured quickly and on a large scale for a therapeutic purpose and used in injectable form or grafted on killer lymphocytes to guide the latter towards the tumor. Strangely enough, another type of B cell, different from the one mentioned above, also infiltrate tumors but is associated with poor cancer prognosis. We shall also study those cells.
Makoto MIYARA
Plateforme de cytométrie AP-HP Sorbonne Université – Hôpital de la Pitié-Salpêtrière – PARIS
We aim to strengthen our flow cytometry platform within the Immunology Department at Pitié-Salpêtrière. Our ultimate goal is to improve the standard of care of patients with autoimmune diseases and those treated with immunotherapies: through more detailed and holistic analyses, we can enable our clinical colleagues to provide more accurate diagnosis, better monitoring, and thus, improved overall patient care.
Our platform encompasses two development projects in biological immunology linked to the acquisition of the FACSDiscover S8, exploring two key dimensions of patient care: diagnosis and prediction of the effectiveness of immunotherapies.
Roberto MALLONE – François BATTEUX
INSERM U1016 – Institut Cochin -PARIS
The incidence of type 1 diabetes (T1D) continues to rise, particularly in children. This autoimmune disease completely destroys pancreatic β cells and requires lifelong insulin treatment. It is possible to detect the autoimmune attack by measuring autoantibodies before this destruction, and thus delay it, particularly in relatives of patients who are more at risk. Such screening requires a simple, high-throughput assay, ideally on samples collected all over France, outside specialized hospitals. The aim of this project is to acquire an automated assay system to develop a pilot project for the early diagnosis and management of T1D, by measuring autoantibodies on blood drops self-collected by finger prick at home and sent by mail.
Valentine FERRE
INSERM IAME UMR1137 – Service de Virologie – Hôpital Bichat – Claude Bernard – PARIS
Screening for precancerous lesions of the cervix and anus is based on the detection of papillomavirus (HPV), which is a highly sensitive technique, but HPV infections are frequent and the development of markers to identify which lesions are most at risk of progression to cancer is crucial. HPV infection can induce aberrant methylation patterns in the cell genome, which are involved in carcinogenesis. Methylation quantification could enable to prevent overtreatment of lesions that are not going to progress while patients with the most high-risk lesions could be treated in priority. The aim of the MetAna project is to automatized methylation quantification, which is currently manual and very cumbersome, to make it accessible and usable in large-scale screening for ano-genital HPV-induced cancers.
Nathalie CHAPUT
UMS AMMICa – Gustave Roussy – VILLEJUIF
EZH2 inhibitors are recent drugs that could improve treatments for certain resistant cancers. EZH2 is an enzyme that helps tumor cells survive by modifying their DNA organization and blocking certain immune defenses. By inhibiting it, tumors could become more vulnerable to the immune system. These drugs appear to work by stimulating mechanisms that mimic a viral infection, prompting the body to react more strongly against cancer cells. They could also promote the emergence of new targets for immune cells, helping the body’s defense system better recognize and attack the tumor. Additionally, EZH2 inhibitors may alter the behavior of immune cells, particularly by influencing the activity of T cells, which play a crucial role in fighting cancer. However, these effects are still not well understood in humans. Further research is needed to better understand their impact and to effectively combine them with other immunotherapy treatments.
Maria-Chiara MIURI
Core Facility CHICS, UMRS 1138 – Centre de Recherche des Cordeliers – PARIS
In the field of immuno-oncology, spatial biology is used to study the immune response against cancer cells and to understand how different types of immune cells interact with tumour cells. Multiplexed immunofluorescence is a technique used in spatial biology to simultaneously detect and visualize several molecules of interest in a tissue sample. It can be used to map different immune cell populations in a tumour context, and to analyse the expression of several specific markers. The aim of this project is to acquire an equipment, that will be mutualized in the CRC Core Facility CHICS, capable of exploring several biological markers simultaneously, opening up new perspectives on the complexity of cancer biology. The “HighPlex” represents a major and essential technological advance for immuno-oncology studies, which explains the strong growth in demand for these technologies. The required equipment will meet these technical needs. It will allow us to study the active immune response against cancer, the expression of specific molecular markers involved in the immune response and to identify potential targets for new immunotherapies.
Emmanuel DONNADIEU
INSERM UMR-1186 – Gustave Roussy – VILLEJUIF
CAR-T therapies, which use genetically modified immune cells to fight cancer, have revolutionized leukemia and lymphoma treatment but remain largely ineffective in solid tumors such as sarcomas. This project aims to understand why CAR-T cells struggle in these tumors, focusing on dedifferentiated liposarcoma (DDLPS) and rhabdomyosarcoma (RMS).
Using a spinning disk confocal microscope, we will observe in real time how CAR-T cells move, activate, and kill cancer cells in fresh tumor slices. We will also explore innovative strategies to enhance their effectiveness, including engineered macrophages (CAR-M) that reshape the tumor microenvironment to support CAR-T function.
This research, part of the Cancer Grand Challenges NexTGen consortium, could support novel immunotherapies and future clinical trials in France.
Camille BIGENWALD
INSERM UMR1015 – Gustave Roussy – VILLEJUIF
This project aims to advance T-cell immunotherapy for cancer treatment through translational research and clinical implementation at Gustave Roussy. The goal is to overcome current challenges limiting access and efficacy by:
1. Developing in-house production of CAR-T cells and tumour-infiltrating lymphocytes (TILs). The initial proof of concept will be conducted in the context of treating refractory autoimmune diseases with CAR-T cells.
2. Modulating the host based on the results of the PIONEER study.
3. Reprogramming the ability of T lymphocytes to resist exhaustion.
Our CAR-T and TIL production facilities will enable clinical trials to be conducted within two years. A Phase I/II clinical framework will guide the translation of CAR-T and TIL therapies, incorporating biomarker-based monitoring and regulatory validation to accelerate patient access.
Quentin PASCAL
UMR1184, IDMIT – CEA – FONTENAY AUX ROSES
Sjögren’s disease is a systemic autoimmune disorder that affects the salivary glands, and in 5% of cases can lead to the development of lymphoma. In the vast majority of cases, this B lymphoma develops from an autoreactive lymphocyte. This is a major illustration of the link between autoimmunity and cancer. The aim of the project is to study the role of the microenvironment in this tumor transformation, notably through immunofluorescence and spatial transcriptomics analyses of salivary gland biopsies. A central hypothesis is that the NF-κB pathway is involved in lymphoma induction. The project will compare the microenvironment of biopsies from patients with Sjögren’s disease, with or without lymphoma, to identify morphological and transcriptomic criteria associated with this transformation. The pathways identified by this approach will then be confirmed in two models: transgenic BAFF mice, spontaneously developing B lymphomas and Sjögren’s disease, and organoids derived from patient biopsies. This work will enable us to evaluate new drug candidates and consider new therapeutic options.
Isabelle PLO-AZEVEDO
INSERM U1287 – Gustave Roussy – VILLEJUIF
Blood cells are particularly difficult to genetically modify in the laboratory. Conventional methods are often inefficient or lead to significant cell death. Viral vectors can overcome some of these limitations, but these approaches are expensive, time-consuming, and require specialized infrastructure.
Lipid nanoparticles, notably highlighted by the mRNA vaccines developed against COVID-19, represent a promising alternative. They can efficiently deliver genetic material or therapeutic molecules into cells with limited toxicity. This technology could greatly facilitate research in hematology and other diseases by enabling larger-scale experiments and opening new therapeutic approaches.
Antonella MERLOTTI-IPPOLITO
INSERM U1356 – Gustave Roussy – VILLEJUIF
Colorectal cancer liver metastases are common and difficult to treat, especially when surgery is not possible. This project aims to develop new immunotherapies able to activate the immune system directly within liver metastases.
To achieve this, we will use lipid nanoparticles carrying messenger RNA to induce the local production of molecules that activate T cells and NK cells against tumor cells. In parallel, we will identify new targets specific to liver metastases, including antigens derived from transposable elements, in order to design more precise therapies.
The requested equipment will allow us to monitor tumor cell killing in real time and better understand how these new immunotherapies work. This project could pave the way for more effective, more targeted, and potentially less toxic treatments for patients.
Charles TRUILLET
BioMaps – U1281 – CEA – Université Paris Saclay – ORSAY
Cancer remains one of the leading causes of death worldwide, and many patients still develop resistance to existing therapies. Targeted radionuclide therapy is an innovative approach that uses molecules able to specifically recognize cancer cells and deliver small amounts of radiation directly inside the tumor. This strategy helps destroy cancer cells while minimizing damage to healthy tissues. The goal of this project is to develop and evaluate new molecules that can both detect tumors and treat them, using advanced molecular imaging technologies. The acquisition of a new preclinical imaging system will allow researchers to precisely track how these treatments distribute within the body and to assess their therapeutic effects.
In the long term, this research could contribute to the development of more precise and personalized cancer treatments, helping accelerate their translation toward clinical applications for patients.
Guido KROEMER
Plateforme AMMICa – Gustave Roussy – VILLEJUIF
So called ‘omics’ technologies, such as genomics, transcriptomics, proteomics and metabolomics are widely used to better understand the biological mechanisms of cancer. They help identify new therapeutics targets, discover biomarkers useful for diagnosis and disease monitoring, and assess treatment effectiveness.
Single-cell analysis is now commonly used in genomics, transcriptomics, and proteomics both in research settings and in the study of patient samples, particularly in specialized laboratories. Metabolomics, which examines the small molecules produced by cells, is especially informative for studying cancer cells and immune system cells. Its development at the sigble-cell level is essential for better understanding the interactions between tumors and the immune system and for designing new strategies to strenghten immune defenses against cancer. This technological platform will play a key role in driving innovation at the Gustave Roussy Cancer Campus and accross the oncology ecosystem of the Ile-de-France Region.
Chiara MAIURI
INSERM UMRS 1138 – Centre de recherche des Cordeliers – PARIS
In the field of immuno-oncology, researchers aim to understand how the immune system recognizes and fights cancer cells. To make progress in this area, it is essential to observe in real time how tumors develop and how immune cells interact with cancer cells within living organisms.
This project aims to acquire a multimodal in vivo imaging system which allows non-invasive visualization of biological processes by combining bioluminescence, fluorescence, and computed tomography imaging. This technology will enable researchers to monitor tumor progression, track immune cell distribution, and evaluate the effects of new treatments in preclinical models.
The instrument will help scientists better understand the immune response against cancer, analyze the expression of molecular markers involved in this response, and identify potential targets for new immunotherapies.
The system will be installed at the Cordeliers Functional Explorations (CFE) core facility of the Centre de Recherche des Cordeliers (CRC) and will be accessible to the wider scientific community. This acquisition will strengthen cancer research capabilities and support the development of innovative therapeutic strategies while respecting the ethical 3R principles aimed at reducing and refining the use of animals in research.
Judith MICHELS
INSERM U1356 – Gustave Roussy – VILLEJUIF
The BioHPV project aims to improve the prevention and treatment of human papillomaviruses (HPV) induced tumors, while exploring the interactions between microbiota, immunity, viral infection, and tumor development.
Persistent HPV infection is the necessary cause for the development of precancerous lesions, which can progress to cancer. These HPV cancers account for 5% of cancers worldwide, affecting women by 90%, with however in western countries an increasing incidence of anal and oropharyngeal cancers mainly in men. This randomized phase 3 trial is evaluating the efficacy of the nonavalent vaccine in 984 patients receiving first-line treatment for precancerous lesions, regardless of the affected mucosa. The goal is to provide robust scientific evidence to expand vaccine indications.
The innovation is based on the study of HPV directed cellular immunity, microbiota (vaginal, intestinal, oral) and the skin virome. Certain microbial profiles influence immunity, the persistence of HPV infections, and their progression to precancerous and cancer lesions. Understanding their impact on vaccine efficacy paves the way for new therapeutic avenues. The immunogenomic approach will enable personalized treatments to be tailored to restore the microbiota and optimize the efficacy of vaccination and anti-tumor therapies.
Audrey PAOLETTI
INSERM U1184 – IDMIT – Université Paris Saclay – KREMLIN-BICETRE
Modern treatments that modify the immune system, known as immunotherapies, have profoundly transformed the management of many autoimmune diseases and cancers. However, these therapies do not affect all patients in the same way: while some respond very well, others develop significant side effects.
The MOSAIC project aims to better understand the role of specific immune cells, called monocytes and macrophages, in these treatment responses. These cells play a key role in regulating inflammation, defending against tumors, and maintaining immune system balance. Researchers will analyze these cells using samples from patients with autoimmune diseases or cancer who are receiving different immunotherapies. The goal is to identify immune signatures that may help explain why some patients respond well to treatment while others develop adverse effects.
To achieve this, the project relies on advanced technologies for analyzing immune cells. The results are expected to improve our understanding of the links between autoimmunity, cancer, and immunotherapies, and could contribute to the development of safer and more personalized treatments for patients.
Nathalie MIGNET
UMR CNRS 8258 INSERM U1267 – Université Paris Cité -PARIS
In 2020, colorectal cancer was the second leading cause of cancer deaths worldwide. This high ranking is partly due to its ability to suppress or evade the host’s immune system. Developing simple screening methods that realistically model tumors and their interaction with immune cells is a crucial current challenge. These new alternative lab methods can reduce risks in drug development while minimizing or avoiding the use of animal models.
Our project proposes an easy-to-produce, customized microfluidic system for high-content screening. By combining advances in microfluidic engineering, we offer a cost-effective approach to study large numbers of tumor spheroids in a thermoplastic environment, optimized for microscopy. This technological leap will help to identify effective combinations of chemotherapy and immune modulators, advancing the fight against colorectal cancer..
Bernard DO
Département de pharmacie clinique – Gustave Roussy – VILLEJUIF
Immunotherapy has transformed cancer treatment by stimulating the immune system to fight tumors. However, some drugs such as ipilimumab (an anti-CTLA4 antibody) can cause significant immune-related side effects when administered throughout the body. Our project aims to make these treatments both safer and more effective by injecting them directly into the tumor instead of delivering them systemically. We are developing biodegradable nanoparticles that encapsulate the drug and release it gradually within the tumor. This strategy is expected to increase local effectiveness while reducing harmful systemic side effects. The acquisition of a dedicated microfluidic manufacturing system within the Gustave Roussy hospital pharmacy will enable the safe, reproducible production of these innovative formulations under controlled conditions, supporting their translation into an early-phase clinical trial. By strengthening the translational infrastructure in Île-de-France, this project will accelerate the development of locally delivered immunotherapies and improve patient access to next-generation cancer treatments..
Makoto MIYARA
Plateforme de cytométrie AP-HP Sorbonne Université – Hôpital de la Pitié-Salpêtrière – PARIS
The immune system must maintain a delicate balance: it needs to be strong enough to fight infections and cancer cells, while remaining controlled enough to avoid attacking the body itself. Regulatory T cells, known as Tregs, play a central role in this balance. When they do not function properly, autoimmune diseases may develop; when they are too active in tumors, they can suppress the immune response against cancer.
The MASSTREG project aims to better understand the diversity of Tregs in cancer and autoimmune diseases. Using mass cytometry, a powerful technology that can measure many cellular features at the same time, we will identify the different Treg states, their stability, and how they change during disease.
The goal is to discover new biomarkers and therapeutic targets that could help predict disease course and support the development of more precise and personalized treatments.
Florent GINHOUX
INSERM U1356 – Gustave Roussy – VILLEJUIF
The main projects we aim to address target several major challenges in immuno-oncology.
First, we focus on diffuse midline gliomas (DMG), aggressive pediatric brain tumors with bad prognoses (less than 10% survival at two years). These cancers remain poorly understood and require in-depth exploration. Our goal is to study the role of microglia (brain’s resident macrophages) in disease progression and treatment resistance. Using innovative models such as organoids (tumor avatars), we seek to characterize the underlying immune mechanisms to identify new therapeutic targets.
Simultaneously, we intend to leverage this technology to investigate hepatic macrophages (Kupffer cells) involved in the metastatic processes of pancreatic cancer, one of the deadliest cancers today. By deciphering their diversity and function, we hope to develop modulatory therapies capable of improving patient outcomes and care.
Myriam MORCEL
Fédérations Hospitalo–Universitaires FHUs (DRCI) – KREMLIN-BICÊTRE
The Workshop Women in Science-Medecine or ‘WiS’ is a workshop organised by the Federations Hospitalo-Universitaires (FHUs). Lasting half a day, the WiS workshop aims to inspire participants and give them the means to take action in their personal and professional lives.
David KLATZMANN
UMRS959 – Laboratoire Immunologie Immunopathologie Immunotherapie – KREMLIN-BICÊTRE
Regulatory T cells (Tregs) are important therapeutic targets for many immunopathologies. Stimulating Tregs with interleukin-2 (IL-2), the key cytokine supporting Treg fitness, is being actively developed. IL-2 is very well tolerated and activates regulatory T cells, inducing a therapeutic effect in several autoimmune diseases. We have been the pioneers for this therapy which is now widely investigated by many academic researchers and companies. In order to foster interactions in the field, we have initiated a very unique international conference entirely dedicated to the biology and therapeutic use of IL-2 in autoimmune diseases, inflammatory diseases, allergy, Treg cell therapy, transplantation and cancer.
Marc SANSON
Siric CURAMUS – Institut du Cerveau – PARIS
Primary brain tumors are among the most resistant cancers to immunotherapy due to the composition and specific organization of the microenvironment, ie the noncancerous cells present within the tumor that interact with tumor cells to constitute the tumor. Recent major advances in understanding these interactions and complex organization, offer real therapeutic hopes. To report on this, we have brought together a panel of top scientists in the field, while also giving ample space to works carried out by junior researchers. This event will be open to researchers, clinicians, students, as well as patient partners of the CURAMUS SiRIC, organizer of the meeting. We hope to foster new collaborations to identify new therapeutic avenues, generate interest, attract young researchers, and disseminate information to patients and the public.
François-Xavier DANLOS
INSERM CIC1428 – Gustave Roussy – VILLEJUIF
The iTox symposium is an annual event designed to bring together experts on immune related adverse events of cancer treatments. It aims to educate students and doctors, enhance knowledge on immunotherapies, and encourage interdisciplinary exchanges to initiate collaborations. Each session expands the discussion to new immunotherapies, including this year bispecific T cell engager treatments and cell therapies beside to immune checkpoint blockade antibodies. The goals are to improve the management of side effects and to stimulate innovation in patients with cancer care.
Marion ALCANTARA
Institut Curie – PARIS
Immunotherapy is the greatest recent breakthrough for cancer treatment. In this context, the FITC (French Society for ImmunoTherapy of Cancer) was created to bring together all stakeholders involved in cancer immunotherapy. Training young clinicians and researchers is at the center of FITC’s missions, to foster innovation and continuously improve the use of immunotherapies for cancer patient care. This unique program was designed to train future leaders in immuno-oncology to develop and manage ambitious research projects with high-impact potential, through a 2-day personalized support from a committee of leading experts in the field with complementary expertise.
Julie HELFT
Inserm U1016, CNRS 8104 – Institut Cochin – PARIS
The Francophone Club of Dendritic Cells (or French Dendritic Cell Society) aims to promote the development of research on dendritic cells and macrophages in both humans and animals, in normal and pathological contexts. It also seeks to foster exchanges among researchers and professionals involved in scientific studies on these cells and their therapeutic applications in humans. Every two years, we organize a scientific conference where national and international experts share their latest advancements with an audience of experienced researchers and emerging young scientists. This event provides our association with an opportunity to highlight research on dendritic cells and macrophages, allow young French researchers to interact with renowned specialists, and showcase French research, particularly that of institutes in the Île-de-France region, to researchers from other regions of France, Europe, and the United States.
Ariane LAPARRA
INSERM CIC1428 – Gustave Roussy – VILLEJUIF
Immunotherapy is the greatest recent breakthrough for cancer treatment. In this context, the FITC (French Society for ImmunoTherapy of Cancer) was created to bring together all stakeholders involved in cancer immunotherapy. Training young clinicians and researchers is at the center of FITC’s missions, to foster innovation and continuously improve the use of immunotherapies for cancer patient care. This unique program was designed to train future leaders in immuno-oncology to develop and manage ambitious research projects with high-impact potential, through a 2-day personalized support from a committee of leading experts in the field with complementary expertise.
