Tumor Biology and Microenvironment Program

The overarching goal of the Tumor Biology and Microenvironment (TBM) Program is to investigate tumor cell-autonomous (intrinsic) processes that underlie signaling pathways and cancer stemness and tumor cell-extrinsic mechanisms by which stromal niche factors and immune components modulate malignancy. Advancing the HICCC’s strategic focus on fostering impactful discovery science and accelerating translation to innovative clinical research, Members pursue studies of novel immunotherapies and other stromal-targeted therapeutics and incorporate new findings and innovative approaches (e.g., 3D organoid cultures) for translation to pre-clinical applications and development of early-stage clinical trials. Co-Leaders, Michael Shen, PhD, Barbara Pro, MD, and Timothy C Wang, MD, bring complementary expertise to the Program’s 64 Members who, in 2024, held $24M of cancer-focused peer-reviewed funding (+45% from the previous renewal), with $10M (42%) from NCI (more than doubled since the previous renewal), $11M (47%) from other NIH sources, and $2.6M (11%) from other peer-reviewed agencies. Members published 548 peer-reviewed cancer research papers over the project period, of which 17% were intra-programmatic, 32% inter-programmatic, and 82% inter-institutional. Notably, 45% were in journals with impact factors >10 and 23% (of total) >20. TBM Program Member-led clinical trials accrued 558 subjects to interventional trials, of which 18% were to investigator-initiated. The TBM Program pursues three interrelated Specific Aims: (1) Investigate stemness and plasticity through studies of cell intrinsic processes that drive tumor initiation and malignant progression to identify strategies to target these processes; (2) Analyze the stromal microenvironment to understand stromal-epithelial cell interactions and understand how stromal niche components modulate tumor growth; and (3) Investigate the tumor immune microenvironment to elucidate the interaction of immune cell with cancer cells and the mechanisms of resistance to immunotherapy. Working with the Community Outreach and Engagement Office, TBM Program research relevant for the catchment area includes in prostate, breast, liver, hematologic, and head-and-neck cancers. The TBM Program fosters interaction of Members (intra- and inter-programmatic) through meetings and retreats, development funds, support of multi-investigator grant proposals, Shared Resources, and strategic faculty recruitments. TBM Program Co-Leaders and Members also play key role in Cancer Research Training and Education Coordination, with mentorship of early-stage researchers through training grants, fellowships, and career development awards. Future goals of the Program include strategic recruitment of senior and junior faculty focused on the cancer stem cells and the tumor microenvironment, as well as increased focus on therapies that target tumor cells and the microenvironment (e.g., cell and gene therapy) and translation of discoveries to clinical trials.