Research conducted in collaboration with Alex Duval’s team (Inserm UMRS 938, Saint-Antoine Hospital Research Center, Paris) allowed us to better assess the impact of the tumor microenvironment on the prognosis of colorectal tumors. This work also may explain why certain immunotherapies are effective in a particular population of patients with colorectal cancer.

The tumors contain both tumor cells and non-tumor cells. The latter form the « tumor microenvironment ». The cells of the microenvironment can have a major effect on the evolution of the cancerous disease. For example, it is well known that a strong lymphocyte infiltration, typical of tumors with microsatellite instability (MSI), is a factor of good prognosis in colorectal tumors. Interestingly, metastatic MSI tumors respond very well to immunotherapies designed to activate the immune response of patients by releasing T-cell activity (called immune checkpoint-based therapies). Based on this observation, we studied the microenvironment of colorectal tumors, aiming to evaluate the quality of the antitumour immune response in an extremely comprehensive manner. Our results have shown that, within metastatic MSI tumors, the antitumour immune response can not develop because of a very strong expression of factors inactivating T lymphocytes, which are nevertheless present in a large quantity. In the end, the method developed makes it possible to obtain prognostic information that is more accurate than the sole analysis of lymphocyte infiltration. In the future, it may also be particularly useful in guiding the use of immunotherapy based on immune checkpoint inhibitors in the treatment of colorectal cancer.

L. Marisa, M. Svrcek, A. Collura, et al., The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors. JNCI, 2017. PMID: 28922790