Research Projects

Immuno-oncology traditionally focuses on alpha beta (αβ) T cells, but current immunotherapies have not effectively exploited the MHC-independent tumoricidal potential of γδT cells. γδT cells exhibit regulatory activity in cancer, but rescuing their antitumor activity in coordination with effector αβ T cells could expand the range of immunotherapy-sensitive tumors. However, the mechanisms governing their differentiation from immature myeloid precursors remain incompletely understood. The long-term goal of this project is to exploit the cross-talk between γδT cells and TAMs cells in building a robust, sustained antitumor response against solid tumors and design interventions that enhance the immunostimulatory, antitumor properties of both γδT cells and TAMs. The shared contributions of γδT cells and M2-TAMs in governing antitumor responses by modulating the effector functions of T and B lymphocytes will be defined. The project aims to open two new directions in the field: 1) M2-polarizing potential of γδT cells in ovarian cancer; and 2) whether by rescuing antitumor functions of γδT cells or by depleting γδT cells, we can restore canonical antitumor functions of macrophages and vice versa. The central hypothesis is that spontaneous protective immune response in ovarian cancer TME is dampened by shared immunosuppressive effects of γδT cells and M2-TAMs, while both cell types influence each other to gain immunosuppressive attributes.