PROJECT SUMMARY/ABSTRACT The Tumor Immunology Program (TIM) unites investigators who share a commitment to work collaboratively to advance our understanding of the relationship between cancer and the immune system and to develop innovative and effective immune-based therapeutics. The overarching goal of TIM is to elucidate mechanisms of interaction between the immune system and cancer cells, providing the rationale for more effective approaches to cancer treatment. We focus our efforts on major cancer burdens and disparities in our catchment area, guided by formal interactions with the Community Outreach and Engagement Core (COE), Program meetings and retreats, and close engagement with Disease Management Groups (DMGs) and Disease Centers. TIM Members operate at three levels: (i) Basic research investigating the cellular and molecular mechanisms that regulate the immune response to cancer, (ii) Translational research that advances basic findings into potential therapies and tests these therapies in appropriate preclinical models, (iii) Clinical research that designs and executes clinical trials testing novel immune-based cancer vaccines or innovative immunotherapies. Research is organized around 3 complementary Thematic Aims: Aim 1: To discover basic mechanisms regulating anti-tumor immunity and its evasion by cancer cells, Aim 2: To elucidate the effect of the microbiome on anti-tumor immunity and response to therapy, Aim 3: To develop and implement clinical strategies to enhance the efficacy of immunotherapy. TIM comprise 41 Members, drawn from 10 Departments in NYU Grossman School of Medicine, School of Arts and Sciences, Tandon School of Engineering and College of Dentistry. Members are PIs on 125 funded cancer-related projects, delivering $27.3M in annual direct costs ($7.7M NCI). During the current funding period, TIM members produced paradigm-shifting basic research findings in cancer immunology, and conducted several practice-changing clinical trials. Our research also led to the design of several new immune-based therapeutics, and over the past 5 years TIM physician members accrued 805 patients to interventional therapeutic trials. Several innovative early phase clinical trials emanated directly from basic science research in TIM laboratories. Since 2018, program members published 778 cancer-related papers, many in high impact journals (~27% in journals with IF >15). The program is highly interactive, as exemplified by our 27 active multi-PI grants and collaborative publications (15% intra-programmatic, 28% inter-programmatic, 50% inter-NCI-CC). TIM members have filed 46 patents (13 of which have been licensed) and had 13 patents issued (4 licensed). TIM derives great benefit from being an integral part of PCC. In the current cycle, TIM members received pilot funding from PCC totaling $ $440,663 of CCSG Developmental Funds and $50,000 of Institutional funds, (a total of $490,663), which resulted in 3 publications, 3 new grants, 2 patents...