Lewis Shi, M.D., Ph.D. Lewis Zhichang Shi, M.D., Ph.D., associate professor and director of Radiobiology, UAB Department of Radiation Oncology, and Koikos-Petelos-Jones-Bragg ROAR Endowed Professor for Cancer Research at UAB, has been awarded a $2.06 million R01 grant from the National Institutes of Health (NIH) National Cancer Institute (NCI) to study how T cells control the therapeutic effects of radiation.
The five-year grant entitled “T Cell-intrinsic Metabolic Control of Radiotherapy” is funded through January 2029, and will allow Shi to explore the connection between T cells—the immune cells that defend the body against infection and tumors—and radiotherapy in an effort to overcome underlying mechanisms causing resistance in cancer patients to therapeutic drugs known as immune checkpoint blockers (ICBs).
ICBs are approved by the U.S. Food and Drug Administration (FDA) to treat patients with various types of cancer such as metastatic melanoma and triple-negative breast cancer. Shi said despite the impressive clinical successes of ICBs over the past decade or so, accumulative data show that their overall efficacy may be reaching a plateau due in part to the therapeutic resistance to ICBs, which poses a significant problem to overcome.
The general belief is that ICBs exert their therapeutic effects by rejuvenating tumor-infiltrating T cells. Shi’s lab will attempt to understand how treating cancer with radiation impinges on T cells and in doing so, to identify practical means to effectively engage T cells in the course of radiotherapy.
“These studies will likely reveal for the first time a T cell-intrinsic control of the immunological effects of radiation, which will provide a promising therapeutic foundation to bypass ICB resistance," Shi said. "We are excited and highly appreciative that NIH-NCI will grant our lab this five-year R01 to delve deeper into this line of research.”
Collaborators on this study include James A. Bonner, M.D., Merle M. Salter Endowed Professor and chairman, UAB Department of Radiation Oncology, and Zechen Chong, Ph.D., associate professor, UAB Department of Genetics and UAB Department of Biomedical Informatics and Data Science.
“Our study may guide future clinical trials testing combinatorial regimens of radiotherapy and immunotherapy, particularly immune checkpoint blockade (ICB),” Shi said. “It will also provide insightful information to direct rational combinations of FDA-approved drugs with radiotherapy and/or immunotherapy to overcome ICB resistance, which has been a pressing unmet medical need.”