The major focus of Dr. Lionel Apetoh’s research laboratory is to investigate the relationships between T lymphocytes and anticancer immune responses. We are searching for novel molecular targets that can be exploited to endow T cells with superior anticancer activity.
The treatment of cancer has for decades solely relied on surgery, radiotherapy, chemotherapy, and hormonotherapy. The therapeutic success of these therapies was exclusively attributed to their abilities to eliminate tumor cells. This contention was however recently challenged, and it is now clear that optimal therapeutic effects of anticancer therapies require a functional immune system. The Apetoh Lab now focuses on the identification of the molecular signals that trigger T cell dependent anticancer immune responses. We specifically investigate how two major cell types essential for the development of adaptive immune responses, CD4 and CD8 T cells, could be therapeutically exploited in cancer. Effector CD4 T cells were initially classified into TH1 and TH2 cells. Novel subsets of CD4 T lymphocytes have since then been identified, including IL-9-producing TH9 cells, which mediate potent anticancer activities upon transfer in vivo. However, the mechanisms regulating their development remain incompletely defined. The first aim of the Apetoh Lab is thus to characterize effector CD4 T cells in mouse and humans to contemplate their use in anticancer adoptive T cell therapy.
The second aim of the lab is to restore the functionalities of CD8 T cells in cancer. In the past years the treatment of metastatic lung and skin cancers has been revolutionized by the use of molecules that restore CD8 T cell anticancer functions, immune checkpoint inhibitors. However, most patients still do not respond to these treatments because of resistance mechanisms that remain to be unlocked. To discover novel molecular targets that can be therapeutically exploited to enhance CD4 and/or CD8 T cell functions, the lab combines in vitro and in vivo approaches such as advanced gene expression analysis of T cells, immunological investigation of the anticancer responses as well as use of transgenic, gene-deficient mice as well as spontaneous and transplantable models of cancers.