Laboratoire d'immunologie et d'immunothérapie des cancers - COMUE Université Bourgogne Franche-Comté

Laboratoire d’immunologie et d’immunothérapie des cancers

The laboratory theme is part of the search for new therapies or therapeutic combinations in the fight against cancer. Our research focuses on the sensitizing effect of nitric oxide (NO) on the death of tumor cells induced by anticancer drugs and the molecular mechanisms responsible for this effect. On the other hand, new molecules, as a kinase inhibitor, are also studied for its antitumor capacity.
– We have demonstrated an antitumor efficacy of a NO donor, glyceryl trinitrate (GTN) (a drug widely used in the treatment of angina pectoris) in combination with standard chemotherapy (FOLFOX, Doxorubicin) in murine models of colon or mammary cancer. The analysis of the mechanisms responsible for this effect has shown that this antitumor effect is associated with the ability of GTN to induce immune cell death (ICD), evidenced by the externalization of calreticulin, an endoplasmic reticulum protein involved in ICD. The next part of the project is to understand how the GTN induces the membrane translocation of this protein. Several hypotheses are under study. Catherine Paul leads this project.
We have shown that the antitumor activity of GTN was dependent of the pro-inflammatory cytokine, TNF, suggesting an innovative therapeutic application with a preferred anti-tumor effect for an inflammatory tumor environment rich in TNF. We have elucidated some molecular mechanisms associated with this effect. We are now looking to extend our study to a broader panel of chemo-induced pro-inflammatory cytokines (especially platinum-derived anti-cancer drugs) in the tumor microenvironment. This project aims to study the combination of GTN/platinum derivatives for the treatment of triple negative breast cancer and to determine the associated molecular mechanisms. Stéphanie Plenchette leads this study.
We have shown that a kinase inhibitor prevents colon tumor progression and inhibits their growth in a syngeneic mouse model, suggesting an immunomodulatory role for this molecule. A characterization of the different immune cells involved in this process has shown that this kinase inhibitor promotes an antitumor immune response. The next part of the project is to characterize the signaling pathways responsible for this effect at the level of the immune cell response, such as T lymphocytes, macrophages and immunosuppressive cells as MDSCs. Several potential protein targets are under study. This work is under the direction of Ali Bettaieb