For decades, the treatment of cancer has relied on surgery, radiotherapy, chemotherapy, and hormonotherapy. The therapeutic success of these treatments was exclusively attributed to their abilities to eliminate tumor cells.
This contention has been recently challenged, and it is now clear that optimal therapeutic effects of anticancer treatments require a functional immune system.
The major focus of my 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.
MScUniversity of Strasbourg
PhDUniversity of Paris-Saclay
Postdoc Harvard University
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.
The first aim of my lab is to characterize effector CD4 T cells in mice and humans to contemplate their use in anticancer adoptive T cell therapy. 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 second aim of our lab is to restore the functionalities of CD8 T cells in cancer. 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. Most patients, however, 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, our lab combines in vitro and in vivo approaches, including:
Challenging the view that chemotherapies only mediate their anticancer activity through a direct cytotoxic activity on tumor cells, my PhD work uncovered a critical contribution of anticancer immune responses for the success of conventional therapies. This work prompted the design of novel strategies enhancing the efficacy of anticancer therapies by manipulating the immune system.
During my postdoctoral work at Harvard University, I underscored the relevance of concomitant Tim-3 and PD-1 blockade to prevent T cell dysfunction and restore anticancer immunity.
After returning to France, I set up my laboratory and showed the anticancer properties of a novel subset of CD4 T cells, IL-9-producing TH9 cells, upon adoptive transfer against melanoma.
With funding from the European Commission, I developed multiple models of combination treatments with chemotherapy and immunomodulation to interrogate the relevance of T cells in anticancer cancer immune responses.
