Title: Targeting Immune Microenvironment in Cancer Immunotherapy

Lecturer: Haidong Tang, PH.D.

                UT Southwestern Medical Center, UT Southwestern

Time: AM10:30, May 15, 2017.

Venue: Lecture hall E407, School of Life Sciences. 

Inviter: Prof. Shengcai Lin, Prof. Dawang Zhou

Abstract: Checkpoint blockade therapy has shown unprecedented success in clinical trials for treating many cancers. However, durable responses are observed in only a minority of patients. It is commonly believed that PD-L1 on tumor cells is essential to prevent T cell-mediated killing. But clinical responses were also observed in some patients that were negative for PD-L1 on tumors. By using PD-L1-deficient mouse and tumor models, we found that PD-L1 in tumor cells is dispensable for the responses to checkpoint blockade. Instead, PD-L1 in antigen presenting cells play more important roles and correlate with clinical benefits in patients. Furthermore, we demonstrate that a sufficient number of tumor infiltrating lymphocytes is a prerequisite for the response. By combining in vitro evolution and protein engineering, we developed an immunocytokine which is able to overcome tumor resistance to checkpoint blockade by recruiting lymphocytes specifically to tumor. Our studies provide new insights to the mechanisms, as well as potential strategies to improve current cancer immunotherapies.