It has become widely accepted that the presence of intraepithelial CD8+ T cell correlate with improved patient survival. In contrast, tumors largely devoid of immune infiltrations or infiltrates skew towards a suppressive phenotype are associated with poor outcomes. In this talk, I will discuss the metabolic constraints imposed by the tumor microenvironment and how this may impact T cell responses against tumors. Specific emphasis will be placed on the condition of hypoxia, its role in the regulation of T cell differentiation, effector function and survival. Initially using ovarian cancer as a disease site, our recently work shows that the tumor microenvironment plays a significant role in dictating the presence and function of T cells. We used a multi-parameter immunohistochemical staining system to co-identify markers of the tumor vasculature and the relative expression of T cells within these regions. We find few T cells co-localizing to areas of hypoxia, whereas most T cells are present in areas of high vascularity. Moreover, there was an association towards improved survival when T cells were detected in vascular environments of the tumor. These observations are consistent with our in vitro work showing that T cells undergoing hypoxia-induced autophagy have impaired cytolytic activity. Overall, this indicates that a T cell response requires overcoming the barriers of the metabolic tumor environment and this may have important implications for T cell-based therapies for the treatment of cancer.
Research And Development
Medical Laboratory Technician25%
Manufacturer - Other25%