SUBJECT: Ph.D. Proposal Presentation
BY: Zhou Yuan
TIME: Wednesday, January 18, 2017, 3:00 p.m.
PLACE: IBB Building, 1128
TITLE: Understanding the effect of tumor microenvironment on T cell antigen recognition
COMMITTEE: Dr. Cheng Zhu, Chair (BME/ME)
Dr. Susan Thomas (ME)
Dr. Michelle Krogsgaard (New York University)
Dr. Mandy Ford (Emory)
Dr. Gabe Kwong (BME)


Skin cancer is the most common cancer in the United States, among which melanoma is the most serious type with high mortality rate. Despite the critical role of CD8+ T cells in tumor clearance, their functions in the tumor microenvironment (TME) are impaired by immunosuppressive cells/cytokines, inhibitory receptors, and metabolic restriction. Targeting these pathways were shown to promote tumor clearance, yet unknown mechanisms may still exist curtailing the T cell responses. T cell activation has been shown to be largely determined by the in situ mechanokinetic properties of the binding of T cell receptor (TCR) to peptide-major histocompatibility complex (pMHC), which are sensitive to perturbations of the cellular environment. Our preliminary studies have shown that the molecular interactions involved in T cell antigen recognition are altered in the TME. The present thesis will study the extent of this alteration, how such alteration consequentially suppresses T cell effector functions, and what the underlying mechanisms are. This study aims to address these questions with animal models, highly-sensitive biomechanical assays of single molecules, and other cellular and bimolecular approaches. The outcome will greatly enhance our understanding of the impaired anti-tumor T cell responses and inspire novel strategies for cancer immunotherapy.