Lewis Shi, M.D., Ph.D.

Volunteer Grant funded by the 2018 V Foundation Wine Celebration in honor of John and Biserka Noval

Cancer is a leading global health concern. Until recently, cancer patients are normally treated with surgery, pharmaceutical reagents that can kill tumor cells (chemotherapy), and radiation (radiotherapy). In recent years, scientists and doctors have been trying to improve patients’ own immune function to combat cancer, known as immunotherapy. Cancer cells can fool the immune system by expressing some markers that can inhibit immune function. These markers are called “immune checkpoints”, including CTLA-4 and PD-1. Subsequently, blocking “immune checkpoints” with reagents (anti-CTLA-4 and anti-PD-1) could enhance immune function and result in impressive curative effects in some patients with cancer. Yet, a lot of patients do not respond to anti-CTLA-4 and anti-PD-1. In order to broaden the patient populations that can benefit from these novel reagents, we plan to change the metabolic features of the microenvironment that tumor cells live in. We hope doing this will improve the function of immune cells, which then causes non-responsive tumors to respond to anti-CTLA-4 and anti-PD-1 treatment. Our studies might also identify some markers that can help doctors in selecting the right patients for these therapies. Our long-term goal is to translate our findings from bench to bedside by designing clinical trials to test combination therapies, particularly in cancer patients that have been non-responsive to anti-CTLA-4 and anti-PD-1 therapies.

Location: Case Comprehensive Cancer Center - Ohio
Proposal: Metabolic checkpoints in anti-CTLA-4 and anti-PD-1 immunotherapies
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