Speaker: Riyue Bao, PhD
University of Pittsburgh
About the Seminar
Talk Title: “Decoding Tumor-Intrinsic Mechanisms of Immune Exclusion: From Human Data to Biological Mechanisms and Translational Impact”
Abstract: Immunotherapies have revolutionized cancer treatment; however, the majority of patients do not experience durable clinical benefit. The central theme of my laboratory is to define the tumor-intrinsic molecular and cellular programs that determine response and resistance to cancer immunotherapy. Our work began with the identification of tumor-cell WNT/β-catenin signaling as a mechanism of CD8+ T cell exclusion in melanoma, followed by systematic analyses demonstrating that activation of this pathway and other oncogenic programs is associated with a non-T cell-inflamed tumor microenvironment across human solid tumors. Building on these observations, my laboratory leverages multi-omic, single-cell and spatial biology, quantitative imaging, pathomics, radiomics, and experimentally tractable human models to identify context-specific mechanisms by which tumor cells remodel antitumor immunity.
These studies have revealed oncogenic signaling, metabolic, and cell-state programs that drive spatially immune-excluded tumor states. Mechanisms include tumor-intrinsic p38 MAPK signaling, SREBP1-dependent lipid metabolism, and other tumor-cell programs driving resistance to immunotherapy. To connect computational findings with experimental causality, we have established patient-derived organoid models coupled with genomic and AI-enabled imaging approaches to functionally interrogate these mechanisms in patient-specific systems and evaluate therapeutic strategies. We have translated several of these discoveries into innovative investigator-initiated clinical trials to improve patient lives, where durable clinical benefit was observed. Together, our work establishes an integrative framework in which computational discovery in human tumors generates mechanistic hypotheses, human-derived experimental models enable functional interrogation, and resulting insights are translated directly to benefit patients. More broadly, our goal is to understand the systems-level rules by which tumor cell states organize the surrounding tissue-immune ecosystem and to identify vulnerabilities that can be exploited to overcome immune exclusion and therapeutic resistance.
Event Details
- Date: October 8, 2026
- Time: 3 p.m. to 4 p.m.
- Location: Fifth and Halket Classroom