Philip Lab Members

The immune system has enormous power to detect and eliminate pathogens; however, CD8 T cells specific for (mutated) tumor antigens found within solid tumors are often dysfunctional, allowing tumors to progress. Hallmarks of tumor-specific T cell (TST) dysfunction in mice and humans include the expression of inhibitory receptors (e.g. PD1, CTLA4) and loss of effector function. The clinical success of immune checkpoint blockade and adoptive T cell therapy in some cancer patients demonstrates the potential of TST to mediate anti-tumor responses; however, many patients fail to respond, or their responses are not long-lasting. Therefore, important challenges and questions remain, including how to predict which patients will have long-lasting responses to therapy and how to design new immunotherapies for those patients who do not respond.

My research group seeks to understand how the immune system interacts with developing cancers from the first mutagenic hit initiating carcinogenesis through progression to late-stage and metastatic tumors. We use clinically-relevant genetic cancer mouse models to understand the molecular and epigenetic regulatory mechanisms underlying TST dysfunction and to design and test cutting-edge strategies to override TST dysfunction to improve cancer immunotherapy. Projects aim to (i) elucidate the mechanisms driving early TST dysfunction, (ii) determine how antigen chronicity drives dysfunction programming in TST, and (iii) design and test strategies, including epigenome editing, to reprogram dysfunctional TST for immunotherapy.