Vascular Immunomodulation in Cancer

The exciting recent results of immune therapies have led to a plethora of clinical trials but the therapeutic effects so far are limited to certain tumors, and only to a small subset of patients. One of the reasons is that tumors have several prospects to escape immune surveillance. One major limiting step is the generation of an immune-suppressive tumor vasculature that is inefficient in enabling T-lymphocytes to infiltrate tumors and attack tumor cells. Using vascular and immunemodulating inhibitors in mouse models of cancer, our group observed for the first time that the efficacy correlated with hot spots within tumors in which the vasculature undergoes dramatic changes and enables immune cells to enter and attack the tumor. These centers are normally found in lymphoid structures where they help lymphocytes cells to get educated in recognizing foreign organisms including tumor cells. By studying the nature, function and regulation of these vascular immune hotspots in tumors, the overarching goal of this proposal is to identify and exploit therapeutic strategies that will generate these tertiary lymphoid structures in tumors as well as in metastases to broaden and enhance the benefits of immune-and other cancer therapies in patients.