PROJECT SUMMARY (ABSTRACT) The Tumor Immunology and Immunotherapy Program (TII) at the Roswell Park Comprehensive Cancer Center encompasses a comprehensive scope of immunology research, from basic mechanistic studies to clinical applications. Our work is grounded in the understanding of harnessing the immune system to prevent and treat patients with all types of cancer, aligning with the Institutional mission to pioneer innovative therapies through immuno-oncology (IO) research. TII has a rich history of translating its research discoveries into patient care, supported by strong collaborations within and across Institutes and working closely with our Community Outreach and Engagement (COE) team. We are committed to focusing on cancers with high incidence rates in our catchment area, ensuring that our research targets the most pressing health concerns and the diverse patient population of the communities we serve. These basic, translational, and clinical initiatives will continue to expand due to multiple ongoing major team science grants and new faculty specializing in active and cellular immunotherapies. To achieve these objectives, TII's research is driven by three core Specific Aims: 1) identifying key mechanisms driving the host antitumor immune response; 2) understanding therapeutic resistance barriers to effective antitumor immunity; and 3) developing and testing novel immunotherapy strategies for both solid and hematologic malignancies. Drs. Scott Abrams and Emese Zsiros co-lead the TII program, each bringing their unique strengths. Dr. Abrams' leadership focuses on the basic and preclinical components of the Program, which unites closely with Dr. Zsiros' leadership, which focuses on the translational and clinical research initiatives. Our program includes 30 members from 11 Departments, with annual peer-reviewed direct funding of $13.5M, $10.9M of which is from the NCI. TII faculty actively participates in several major team science grants, including the renewal of the Roswell Park-University of Chicago Ovarian Cancer SPORE. Altogether, TII faculty serves as PD/PI on four (i.e., P50, P01, U01, and DoD Breakthrough Level 4), MPI on three (i.e., 2 additional U01's and 1 U24), and Project Leader on two (i.e., a second P50 and a second P01) major team science awards. Of 756 publications to date, 34% are high impact (IF>10), with 50% and 57% involving inter-program or inter- institute collaborations, respectively. TII maintains a robust clinical trial portfolio with >1,000 interventional treatment accruals during this funding period. TII faculty also lead or co-lead multiple training grants and actively partners with the Cancer Research Training and Education Coordination core aiming to mentor the next generation of IO scientists. We stand committed to fostering a diverse academic environment by recruiting an array of faculty, with a special emphasis on underrepresented minorities, to enrich our perspectives and enhance our collective expertise. With a strong funding base, the expertise of our faculty, and robust collaborations, TII is well-positioned to continue advancing IO-based discoveries and developing innovative therapeutics.