Jedd Wolchok, MD, PhD, FASCO

Improving response to immunotherapy in breast cancer patients.

Impact

Immunotherapy is a treatment strategy that utilizes the body’s immune defenses to fight disease. Immune checkpoint blockade (ICB) is an innovative cancer treatment that uses a class of drugs known as immune checkpoint inhibitors that are designed to help the immune system recognize and destroy cancerous cells. This treatment strategy has been effective in patients with melanoma, lung, and other cancers, but has not been very effective for most breast cancers. The BCRF-supported research of Drs. Wolchok and Merghoub focuses on both developing new immune-based strategies and improving response to existing immunotherapies in breast cancer.

Progress Thus Far

Previously, Drs. Wolchok and Merghoub pioneered approaches targeting tumor metabolism to restore anti-tumor immunity. They found that inhibiting an enzyme called lactate dehydrogenase increased the availability of glucose, an energy source for T cells, which enhanced response to ICB. The team also found that inhibiting a protein called MCT4 reduced triple-negative breast cancer (TNBC) growth and restored the ability of a certain type of T cell to infiltrate tumors.

What’s next

Drs. Wolchok and Merghoub will continue to develop new metabolic-based strategies to enhance ICB in breast cancer. In the upcoming year, they will evaluate whether making glucose more available improves T cell therapy in TNBC and continue assessing whether inhibiting MCT4 enhances IBC response. To complement this work, they will correlate MCT4 expression in TNBC patient samples with clinical outcomes. The team will also test whether a class of drugs called ferroptosis inducers in combination with their regimen improves ICB in TNBC.