Cancer Microenvironment Research Program

University Of Rochester, Rochester NY

Investigators

Abstract

CANCER MICROENVIRONMENT RESEARCH PROGRAM: PROJECT SUMMARY/ABSTRACT The goal of the Cancer Microenvironment (CM) research program at the Wilmot Cancer Institute (Wilmot) is to understand how tissue microenvironments control cancer initiation, progression, and treatment. In addition to seminal contributions toward the definition of key cell populations in both immune and stromal compartments of cancer, CM members take advantage of direct access to novel genetic models and patient-derived specimens to define key cancer-driven signals that silence cancer immunity or promote malignant stem cells. Leveraging expertise in immunology, stem cell biology, radiobiology, and nanotechnology, the specific aims of the CM program are to: 1) disrupt and reprogram cancer-promoting microenvironments; and 2) restore normal tissue homeostasis from cancer and cancer treatment-induced injury. Together, these overarching goals complement those of the Genetics, Epigenetics and Metabolism (GEM) and Cancer Prevention and Control (CPC) research programs. In collaboration with the Community Outreach and Engagement office (COE), research activities in CM directly address problems associated with the advanced age, rurality, and high cancer incidence in Wilmot’s catchment area. Led by Laura Calvi, MD, and Minsoo Kim, PhD, the CM program consists of 30 members from 19 departments at the University of Rochester. Program members have published 286 cancer-relevant papers since 2019. As of November 1, 2023, CM program members held $5.47 million in annual direct, peer-reviewed, cancer-relevant funding. Recent major achievements include: 1) the inhibition of myeloid suppressive cell populations and reactivation of adaptive immunity via multimodal strategies to decrease tumor burden and even cure locally advanced pancreatic ductal adenocarcinoma (this led to Phase I clinical trials); 2) the identification of critical immune cell interactions within the cancer microenvironment that are being exploited to improve cell-based immunotherapy; 3) the discovery in hematologic malignancies of key targetable interactions in the bone marrow microenvironment that mitigate transformation and improve hematopoietic fitness (this is already being tested in investigator-initiated clinical trials); 4) upfront checkpoint inhibition in Hodgkin lymphoma to enhance cures and minimize radiotherapy; and 5) the establishment of in vivo models and mechanisms of radiation-induced acute and late tissue dysfunction and their mitigation that are being leveraged to enhance treatment efficacy and reduce morbidity in cancer survivors. The CM program strives to exploit these novel findings toward clinical translation through interaction with Wilmot’s Disease Working Groups and Translational Research Groups, particularly in the areas of myeloid and lymphoid malignancies, pancreatic and gastrointestinal malignancies, and immunotherapy and radiotherapy. Overall, the CM program promotes center-wide goals for improvements in cancer outcomes in Central and Western New York by uncovering key mechanisms underlying interactions of cancer with its microenvironment to enable new targeted therapeutic opportunities.