Cancer Immunology Program Project Summary / Abstract The mission of the Cancer Immunology Program is to identify mechanisms that regulate the anti-tumor immune response and translate this information into efficacious immunotherapies for cancer patients. The central hypothesis of the program is that a deeper understanding of the requirements for effective innate and adaptive host responses will advance development of treatment strategies that overcome tumor immune escape. Program members collaborate extensively across all DF/HCC programs and institutions. The Program supports an active clinical immunotherapy trials program, especially investigator-initiated clinical trials, across multiple DF/HCC institutions in immune checkpoint blockade, cancer vaccines, immunoregulatory monoclonal antibodies, and adoptive cellular therapies, including CAR T cells. The Program’s 116 members (76 primary and 40 secondary) represent all seven DF/HCC institutions and 15 academic departments. In 2019, peer-reviewed grant funding attributed to the Program was $5.8 million in direct costs from the NCI and $9.8 million from other sponsors. During the current funding period, Program members published 985 cancer-relevant papers. Of these, 28% were inter-institutional, 16% were intra- programmatic, and 44% were inter-programmatic collaborations between two or more DF/HCC members. The breadth of inter-Program interactions speaks to the impact of Cancer Immunology across a large spectrum of human cancers. For the next CCSG funding period, the Program’s Specific Aims are to 1) Discover innate and adaptive mechanisms of response and resistance to efficacious cancer immunotherapies; 2) Develop and test novel interventions that deepen the impact of cancer immunotherapy; and 3) Define mechanisms of immune-related adverse events and enhance the safety of cancer immunotherapies. These Aims align closely with the Center strategic plan and to achieve them Program members will continue to collaborate extensively across DF/HCC Programs and member institutions. An important associated goal is to train and mentor future leaders in Cancer Immunology.