Taylor, MS, and Xiaopeng Sun, who are graduate students in Balko’s lab. The lead authors of the study are Brandie C. However, understanding this gives us a potential biomarker for identifying those patients and, perhaps more importantly, exposes a new way to target the tumor cells that have escaped the immune system,” said Balko, the study’s corresponding author. “These findings shed some light on at least one reason why only a small fraction of breast cancer patients benefit from immunotherapy - their tumors have already found a way to remove a critical component for immunotherapy response. This study deepens the understanding of why immunotherapies are ineffective for many triple-negative breast cancer patients and how to overcome this drug resistance. Their findings suggest that combining anti-NKG2A with anti-PD-L1 therapy may represent a promising, yet underexplored approach for treating triple-negative breast cancer. They then set about exploring how to overcome this therapeutic resistance in patients. This variability was linked with a lack of benefit from the addition of immunotherapy. Analyzing the variability of tsMHC-I in human breast cancers and in mouse models, they found high heterogeneity in the expression of this molecule. In this study, the researchers led by Justin Balko, PharmD, PhD, PharmD, Ingram Associate Professor of Cancer Research, studied tumor-specific Major Histocompatibility Complex I (tsMHC-I), a molecule that is essential to the immune system’s ability to recognize tumor cells. These receptors exist on immune cells (‘natural killers’) capable of destroying cancer cells. The research, published in Cancer Discovery, highlighted NKG2A receptors as potential targets for overcoming immunotherapy resistance in breast cancer. Identifying why most patients don’t respond is critical for personalizing treatment plans and minimizing therapy side effects in patients. Researchers at Vanderbilt-Ingram Cancer Center have discovered a druggable target on natural killer cells that could potentially trigger a therapeutic response in patients with immunotherapy-resistant, triple-negative breast cancer.Ĭurrently, only about 15% of early-stage, triple-negative breast cancer patients benefit from combining immunotherapy, drugs that target immune cells to attack the tumor, with chemotherapy. The study team included, from left, Paula Gonzalez-Ericsson, MD, Xiaopeng Sun, Justin Balko, PharmD, PhD, and Brandie Taylor, MS.
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