PROJECT SUMMARY/ABSTRACT - IMMUNOLOGY AND CANCER (IC) Members of the Immunology and Cancer (IC) Program of the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) aim to understand the interface between the host immune system and a malignant tumor, and to use this knowledge to develop effective immunotherapies for the treatment of a broad array of cancer types. In addressing our 3 specific aims, program members are making fundamental advances in the understanding of anti-tumor immunity and immune regulation, bringing new concepts into preclinical models of anti-tumor immunity, translating fundamental discoveries into clinical applications, and testing new hypotheses generated from human studies back in murine models. Aim 1 is to elucidate fundamental immunology concepts that have relevance for the cancer context. In this regard, we have made key advances regarding the nature of the endogenous T cell response to cancer, the role of the microbiota in impacting myeloproliferative disease, and novel mechanisms of antigen presentation that direct the priming of tumor-specific T cells. Aim 2 is to define mechanisms impacting anti-tumor immunity and evaluate novel treatment strategies in preclinical settings. Here, program members have engineered novel approaches to reduce the toxicity of checkpoint blockade antibodies, enhance the efficacy of CAR-T-based cellular therapies, implement potent adjuvant combinations for cancer vaccines, and augment the efficacy of immunotherapy via manipulation of the microbiota. Aim 3 is to translate fundamental research discoveries into clinical applications and take new clinical observations back into the laboratory. The program has developed key collaborations with clinical researchers from the Clinical and Experimental Therapeutics Program and industry partners to implement numerous interventional immunotherapy clinical trials. Program current efforts are aided by extensive biobanking, recent expansion of our cGMP facility to include a vector production lab, and expansion of infrastructure for executing cell therapy studies using T cell products generated in-house. The IC Program adds considerable value to the UCCCC by fostering an environment that promotes collaboration, focuses basic research on important cancer-relevant questions, and promotes the bidirectional transfer of ideas between the laboratory and the clinic. Program leaders have been pivotal in: (1) the enhancement of tumor immunology research across the UCCCC; (2) the recruitment of senior and junior immunology investigators to the program; (3) the promotion of collaboration among immunologists, clinicians, and basic scientists at UCCCC through intra- and inter-programmatic activities; and (4) the development of the solid tumor cellular therapy program in collaboration with CET leaders in the Jonas Center for Cellular Therapy. In addition, IC faculty play critical roles in advancing local diversity initiatives, participating in community ed...