Finding new regulators of the interaction between CD8 T cells and dendritic cells

Tumors are complex tissue that contains many cell types including immune cells. The observation of tumor antigen-specific CD8 T cells can be detected in cancer patients has dramatically advanced our understanding of tumor immunology and formed the basis for antigen-specific immunotherapy, immune checkpoint blockade (ICB), and CAR T cells. However, most patients still do not respond to immunotherapy, and many patients that do respond often experience relapse. The reasons are not fully understood, but T cells exhaustion/dysfunction due to immunosuppressive signals in the tumor microenvironment and fail to communicate with other immune cells contribute to the poor response. There is a need for a better understanding of the mechanisms of CD8 T cells activation.

T cells priming and activation depend on two signals that can be mediated by dendritic cells (DCs): (i) antigen specific, an interaction between MHC molecule and T cell receptor (ii) antigen independent, an interaction between B7 molecule that express by DCs and CD28 that is being expressed by T cells. Importantly, additional receptor and cytokines including adhesion molecules regulate DCs- T cells interaction and activation but the full landscape is still unknown.

Finding additional key molecules that can be targeted to improve T cells activation can improve the spectra of current immunotherapy treatment. In this study, we will use invitro system to systematically search for such molecules.