Tumor Microenvironment and Cancer Immunology

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ABSTRACT – TUMOR MICROENVIRONMENT AND CANCER IMMUNOLOGY PROGRAM The overarching goal of the Tumor Microenvironment and Cancer Immunology (TMCI) Program is to define how the dynamic interplay among cancer cells, immune cells, stromal components, and vasculature regulates the growth and dissemination of malignancies, and in so doing, identify therapeutic approaches to modulate the microenvironment and tumor growth. The Program consists of 13 faculty (one a new recruit) and five adjunct members, and integrates members whose expertise includes cell migration/invasion, molecular structures, cell signaling, cell metabolism, and angiogenesis, with members whose work encompasses therapeutic targeting of innate and adaptive immune cells, and the influence of the microbiome on tumor- and immune cell-directed cancer therapies. This complementary expertise is organized around three interacting themes: (1) Activating Invasion and Metastasis; (2) Avoiding Immune Destruction, and (3) Tumor Promoting Inflammation. These themes encompass many of the molecular processes that coordinate the formation of the microenvironment that enables progressive tumor growth and metastasis. Members interact on several of levels, including monthly faculty meetings, program-led seminars (48 in the last funding period), strategic meetings organized around new collaborative opportunities (for example, the interface of the human microbiome and cancer), and collaborative grants. Program funding is strong, with current total annual grant funding of $4.4M (direct costs) ($2.6M from NCI, 58%). Members currently lead 28 grants including 15 R01s (nine from NCI), and lead or participate in three P01s (two from NCI), and multiple other grants. Over the last funding period, members have participated in 34 (32%) collaborative grants. Our productivity is reflected in 224 cancer-relevant publications in the last funding period, of which 31% were collaborative (19% intra- and 12% inter-programmatic). In 2018, we published 42 cancer-relevant publications, of which 21% were intra- and 5% inter-programmatic. TMCI members have pioneered novel approaches to interrogate the fundamental properties of tumor cells and other cell types within tumors, and are developing immune cell- and tumor-targeted therapies. Members are participating in translational initiatives through the Oncology Disease Teams, C3 Cancer Center Council, and the San Diego Center for Precision Immunotherapy, which support collaborations with local oncologists to enable large collaborative grants applications. In recognition of the role of the immune system in combatting cancer, a key goal of the Program is to build and further strengthen expertise in cancer immunology by hiring at least two additional faculty, including one with expertise in vaccinology. Key scientific goals are to extend the use of infection models to inform studies to harness the immune system for immunotherapy and cancer vaccines as well as to integrate single-cell transcriptomics, proteomics, epigenetics, and metabolic profiling and imaging of cancer cells, immune cells, and stromal cells in tumors to achieve new insights into the regulation of tumor growth outcomes and cellular processes that lead to drug resistance and immune evasion by tumors.