RESEARCH AREA

This area aims to explore the immunological processes, common or opposed, involved in carcinogenesis and responses to anti-cancer immunotherapies, but also in autoimmune/inflammatory diseases at increased risk of cancer. One of the expected objectives is to identify immunological signatures of cancerous, inflammatory and healthy tissues.

For example, DIM ITAC will investigate :

• Opposing abnormalities in macrophage differentiation: anti-inflammatory in cancer and pro-inflammatory in autoimmune diseases,
• The stimulation of B cells in autoimmune diseases and lymphomas,
• The role of microorganisms in triggering immune responses within cancers and organs affected by autoimmune diseases, triggered or not by cancer immunotherapies,
• The role of autoantibodies and autoantigens,
• The functions and interactions between lymphoid and myeloid subpopulations,
• The role of cytokines, whose action may be different in the context of cancer or autoimmune disease (depletion or activation),
• The role of microRNAs and epitranscriptomic anomalies in both types of disease.

New ex vivo modelling tools for cancer or autoimmune diseases, such as organoids or spheroids of tumours or organs targeted by autoimmune diseases, are currently being developed by network partners as an extremely powerful means of faithfully recapitulating patient characteristics. These innovative cell culture techniques will be used to design and test new anti-cancer or anti-inflammatory immunotherapies on a large scale.

New innovative therapeutic approaches will be evaluated, in particular those that :

• target excessive metabolites or alter epitranscriptomics,
• reduce the immunogenicity of immunotherapies used in cancer or inflammatory diseases,
• are based on modified lymphocytes or monocytes (CAR-T or CAR-mono).

The implementation of therapeutic trials to evaluate new immunotherapies more targeted to cancer or in combination with anti-inflammatory cytokines (TNF, IL-6, IL-4, IL-13) will allow the development of new anticancer or immunological treatments with an optimised risk-benefit ratio.

Therapeutic advances in cancer will be explored in autoimmune diseases (CD3/CD19 or CD3/BCMA bi-specific CAR-T cells). Conversely, anti-cytokines used in inflammatory diseases may be useful to enhance the effect of anti-tumour immunotherapies in cancer by reducing the depletion associated with hyper-inflammation.

Finally, the treatment of immunological side effects of immunotherapies could benefit from therapeutic advances in autoimmune diseases (anti-cytokines, JAK inhibitors, etc.).