Lymph node myeloid cells directing anti-tumor T cell priming

T cells are the main immune effector cells that can kill tumor cells and are therefore critical players in tumor immunology and cancer immunotherapy. Many currently approved cancer immunotherapies for example immune checkpoint blockade are based on boosting T cell effector function. However, in cancer, suppressive mechanisms often dampen the anti-tumor T cell response. We aim to identify suppressive mechanisms in lymph nodes that could yield insights into novel immunotherapy targets. Tumor-directed effector T cells, which can kill tumor cells, are generated in tumor-draining lymph nodes upon contact with myeloid cells. Thus, understanding immunosuppressive mechanisms in the lymph node is key in order to activate effective anti-tumor T cell immunity. We have recently discovered massive infiltration of multiple myeloid cell subsets, including monocytes and neutrophils, into lymph nodes in oral carcinoma. The functionality of those myeloid infiltrates, and whether they have the capacity to regulate tumor-directed T cell immunity, is unknown. We hypothesize that infiltrating myeloid cells are partially immunosuppressive, and that targeting those suppressive myeloid signals could potentiate anti-tumor T cell immunity. In this project, we will investigate the immunosuppressive function of myeloid cells infiltrating tumor-draining lymph nodes. Our objectives are to (1) test the capacity of myeloid populations to regulate T cell activation and differentiation into effector, memory, and exhaustion/dysfunctional lineages; (2) assess what lymph node niches are altered or disrupted by myeloid infiltration to get further insights into their role in shaping functional niches in the lymph node; and (3) proof of the concept of targeting tumor draining lymph node-infiltrating myeloid cells to restore anti-tumor T cell immunity. Results will deepen our understanding of how T cell immunity is initiated in the context of cancer; and will establish tumor draining lymph node-infiltrating myeloid subsets as potential immunotherapy targets.