Tumor-specific T cell immunity (Almeida Laboratory)

Tumor immunotherapy has represented a major breakthrough against different types of cancer. It is now well established that T cells can recognize tumor-expressed antigens and promote an effective anti-tumor immune response, as illustrated by recent advances and clinical trials with T cells expressing a chimeric antigen receptor (CAR) recognizing targets expressed by the tumor. Unfortunately, because tumors are highly heterogeneous and the majority do not express specific, targetable antigens, CAR T cell therapy is only applicable to a small subset of malignancies. We are currently interested in understanding if and how large numbers of autologous tumor-specific T cells can be generated and expanded as a way to promote effective anti-tumor immune responses. We focus not only on cytotoxic T cells (CD8⁺), which can directly recognize and kill tumor cells but also on helper T cells (CD4⁺), which are fundamental for anti-tumor immune responses but not as frequently studied in this context as the former. We believe the ideal T cell-based immunotherapy will benefit from a combination of both tumor-specific CD4⁺ and CD8⁺ cells.

An additional factor that represents a hurdle in tumor immunotherapy is the fact that many tumors are infiltrated by highly immunosuppressive cell populations, including regulatory T cells (Tregs). While fundamental to prevent undesirable (auto)immune responses, intratumoral Tregs are believed to prevent effective immune responses towards tumor antigens, shielding the tumor from the action of pro-inflammatory immune cells. Because many Tregs recognize tumor-antigens, we are also interested in understanding whether these tumor-reactive Tregs can be reprogrammed to lose their suppressor function and be reprogrammed into tumor-specific pro-inflammatory T cells.