CANCER IMMUNOLOGY RESEARCH PROGRAM PROGRAM CODE: CI PROJECT ABSTRACT/SUMMARY The overarching mission of the Cancer Immunology (CI) Research Program is to improve understanding of the immune response to cancer and to discover and test novel approaches to harness the immune response to improve patient outcomes. The Program was ranked outstanding to exceptional in the last renewal. Marcus Bosenberg, MD, PhD, Carla Rothlin, PhD, and Mario Sznol, MD lead the CI Program and are experienced investigators and leaders with complementary expertise, sustained NCI funding, and multiple contributions in cancer immunology. Bosenberg has discovered new approaches for enhancing immune therapies using leading cancer immunology models that his lab developed. Rothlin is an expert in the roles and effects of the innate immune system on anti-cancer immune responses. Sznol is an internationally recognized expert in the clinical evaluation of immuno-oncology therapies and pioneered the use and evaluation of combination immune therapies. CI consists of 57 members from 17 different departments across Yale, including eight members of the National Academy of Sciences, and nine current or former investigators/faculty of the Howard Hughes Medical Institute. The work of the CI Program revolves around three Aims: 1) Identify mechanisms of anti-tumor immune response and resistance; 2) Elucidate the mechanistic links between inflammation and cancer; and 3) Translate fundamental immuno-oncology discoveries into novel therapeutic approaches and biomarkers. CI members published 321 papers during this award period, 47% in high impact journals, with inter-programmatic (42%) and intra-programmatic (14%) publications, demonstrating interactions among CI members within the Program, as well as with YCC members in other programs. During the past funding period, CI experienced a 28% increase in total funding ($17.6M direct), as well as a 46% increase in NCI funding (3.8M direct). Immune therapy for cancer has emerged as one of the most exciting and promising new approaches ever developed to treat cancer. YCC and the CI Program has been at the forefront of the immuno-oncology revolution, playing leading roles in important advances in basic immunobiology, identification of checkpoint inhibitors, development of unique cancer immunology animal models, and FDA approval of immuno-oncology therapies. CI will continue to lead this field as a highly interactive program dedicated to improving understanding of the host response to cancer and developing novel approaches to translate fundamental discoveries to improve cancer patient outcomes. CI will focus on impact in YCC catchment-related malignancies, serving underrepresented populations, and training the next generation of diverse cancer immunology researchers and translationally-focused clinicians.