The VIRONMENT project receives generous support from the MSDAVENIR Fund

After decades of cancer research targeting tumor cells, strategies aimed at targeting the tumor microenvironment (MET) for therapeutic purposes are expanding rapidly. Indeed, it has been demonstrated that the composition and quality of MET have a major prognostic impact and influence the response to antitumor treatments, such as immune checkpoint inhibitors (ICI) and cytotoxic chemotherapies. The immune mechanisms associated with MET and involved in resistance to antitumor treatments have only been partially described and are currently leading to the development of new promising therapeutic approaches.

Cancers associated with viruses are common and constitute a major public health problem. Several viruses are described as associated with cancers, either directly involved in carcinogenesis (oncovirus, example: Human Papilloma Virus (HPV)) or indirectly by inducing, for example, immunodepression favoring the occurrence of cancer (example: Human Immunodeficiency Virus (HPV) HIV)). These viruses seem capable of affecting the molecular profile and the MET of these cancers and thus modifying their sensitivity to antitumor treatments. Some virus-associated METs have been partially described, mainly using transcriptomic and T-cell-centered approaches. Immune mechanisms specifically associated with viruses and involved in resistance to antitumor treatments such as ICIs and chemotherapy have not yet been described.

The objectives of VIRONMENT aim to characterize in depth the METs and the immuno-molecular mechanisms involved in resistance to anti-tumor treatments for cancers associated or not with a virus, in order to:

• Characterize METs specifically associated with viruses using transcriptomic (RNAseq) and proteomic (mass cytometry on tissue sections coupled with the HYPERION imaging system) approaches.
• Identify immune mechanisms specifically associated with viruses and involved in resistance to ICIs and cytotoxic chemotherapies.
• Discover new molecular and immune targets for future MET-based therapeutic strategies for virus-associated cancers.

* VIRONMENT : Microenvironnement tumoral associé aux virus : caractérisation et mécanismes immunologiques de résistance aux traitements antitumoraux.