How MD Anderson is Investigating Mechanisms of Response and Resistance to Immune Checkpoint Therapy

Padmanee Sharma, MD, PhD is a nationally and internationally renowned physician scientist whose  research work is focused on investigating immunologic mechanisms and pathways that  impact tumor rejection. She is a trained medical oncologist and immunologist and the  TC and Jeanette D Hsu Endowed Chair in Cell Biology. Her expertise in Immunology  and Genitourinary Medical Oncology enabled her to design and lead clinical trials with  immune checkpoint therapy for patients with metastatic renal cell carcinoma and  bladder cancer, which led to improved survival and approval of new treatments for these  patients. To understand the impact of immune checkpoint therapy on human immune  responses and to generate preliminary data with immune checkpoint therapy in the  localized disease setting, she designed and conducted the first neoadjuvant (pre surgical) trial with immune checkpoint therapy (anti-CTLA-4) in 2004. These studies led  her to identify the ICOS/ICOSL pathway as a novel target for cancer immunotherapy  strategies. Clinical trials targeting the ICOS/ICOSL pathway are currently ongoing. Dr Sharma continues to design novel clinical trials to evaluate human immune responses  to different immunotherapies and she is the Principal Investigator for multiple  immunotherapy clinical trials that focus on translational laboratory studies. She was the  first to demonstrate that human tumors express VISTA as an immunosuppressive  pathway. Clinical trials targeting VISTA are currently ongoing. She was also the first to  demonstrate that anti-CTLA-4 plus inhibition of EZH2 can improve anti-tumor  responses, which led her to design a new clinical trial with this combination. This clinical  trial is currently accruing patients. As a result of her expertise, MD Anderson Cancer  Center established the Immunotherapy Platform. Dr Sharma serves as the inaugural  Scientific Director of the Immunotherapy Platform and she focuses her effort on a  “reverse translation” process that encompasses studies on human immune responses to generate hypotheses related to mechanisms of tumor rejection, which she tests in  appropriately designed pre-clinical models, and subsequently uses the new data to  design novel clinical trials to improve outcomes for patients with cancer. She is a  Professor in the departments of Genitourinary Medical Oncology and Immunology and  is also the Co-Director of Parker Institute for Cancer Immunotherapy at MD Anderson  Cancer Center. She is a member of the American Society for Clinical Investigation  (ASCI); received the Emil Frei III Award for Excellence in Translational Research in  2016; the Coley Award for Distinguished Research for Tumor Immunology in 2018; and honored with the Women in Science with Excellence (WISE) award in 2020.