January 24, from 12.00 to 13.00
Seminar with Pierre Larrieu
"Two potential pathways to modulate anti-tumor immunity"
The demonstration that tumor specific cytotoxic T lymphocytes (CTL) are major effectors of the surveillance of experimental- and virus-associated human cancers, as well as the discovery of human tumor-associated antigens (TAA) recognized by CTL from patients, initiated twenty years ago, opened the way to developing cancer vaccines to treat non-viral associated cancers. Immunogenic cancers such as melanoma were particularly targeted. Nonetheless, these treatments have not yielded fully satisfying clinical responses so far.
A suggested limit of cancer vaccines, would be their inability to induce an exclusive and sustained cross-presentation by mature DC, which appears mandatory to mount robust cytotoxic T cell responses. The uptake and long term cross-presentation of tumor antigen long peptides (LP) by DC make them attractive cancer vaccine candidates. Our results document for the first time the strong immunogenicity of a human tumor antigen LP.
The cancer vaccines failure has been also attributed to immunosuppresion and tolerance mechanisms, which develop within the tumor environment. We describe a new mechanism of tumoral immune resistance based on expression of an unrelated hepatic enzyme that degrades tryptophan along the kynurenine pathway (Tryptophan 2,3- dioxygenase) and establish proof-of-concept for the use of TDO inhibitors in cancer therapy.