Our research

T cells have the potential to control and eradicate cancer, but in many cases T cells recognizing tumor-specific antigens (also called neoantigens) and recruited to the tumor site fail to achieve tumor destruction due to an immunosuppressive milieu. A powerful strategy to subvert immunosuppression consists in the targeted stimulation of tumor-specific T cells using neoantigen vaccination.

Unfortunately, as to date, the identification of tumor neoantigens is still inefficient, requiring sequencing of tumor tissue and computational prediction which often fails to correctly predict immunogenicity. Here we propose to develop a novel approach for the discovery of tumor neoantigens based on the rapid screening of the TCR specificity exhibited by tumor infiltrating lymphocytes. This approach has the potential to radically improve our ability to design effective neoantigen vaccines for tumors.

Therapies based on Chimeric Antigen Receptor (CAR) engineered T cells and on tumor infiltrating lymphocytes (TILs) represent powerful and targeted immunotherapeutic strategies against cancer. Several preclinical studies have investigated how therapeutic T cells directly impact tumor cells, highlighting their cytotoxic and surveillance capacity.

Nevertheless, because these “living drugs” enter a niche composed not only of tumor cells but also of endogenous immune cells, it is essential to understand how this interplay influence therapeutic efficacy. This project aims to explore the interactions occurring between therapeutic T cells and immune cells in the TME and to characterize their functional consequences on anti-tumor response.

This study will contribute to a better understanding of the anti-tumoral immune response, with findings that can be leveraged for the design of novel therapeutic strategies, that combine tumor killing and the support of the endogenous immune system.