OCT 30, 2014 12:00 PM PDT

The metabolic microenvironment in tumors and its impact on T-cell mediated immunity

Speaker
  • Scientist BC Cancer Agency's Deeley Research Centre, Assistant Professor Department of Biochemistry and Microbiology, University of Victoria
    Biography
      Dr. Julian J. Lum graduated with a PhD in Immunology from the University of Ottawa. He spent five years training at the University of Pennsylvania in the field of cancer biology with special emphasis on tumor metabolism. There he studied how cells adapt to nutrient stress and the role of autophagy in promoting cancer cell survival. In 2008, Dr. Lum returned to Canada and joined the Deeley Research Centre at the BC Cancer Agency, as a Scientist where his current research interest is in autophagy and metabolism of clear cell ovarian adenocarcinoma. He hopes the information gained from this work will enable a better understanding of how the tumor microenvironment influences the immune response to cancer. Dr. Lum is an Assistant Professor with the Department of Biochemistry and Microbiology, University of Victoria. He is also the recipient of a CIHR New Investigator Award. His work is funded by the BC Cancer Foundation, CIHR and Genome BC.  

    Abstract

    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.


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