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Immune cells contribute to treatment resistance in aggressive breast cancers

Modifying the immune environment may make breast tumors more vulnerable to immunotherapy

JCI Journals

Breast cancer remains a leading cause of cancer-related death for women in the United States. Early detection and targeted therapies have improved overall patient outcomes, but these factors also profoundly influence the wide stratification of prognoses. So-called "triple-negative" breast cancers, which lack expression of estrogen, progesterone, and human epidermal growth factor 2 (HER2) hormone receptors, cannot be targeted by existing hormonal therapies and are associated with poor patient survival. The claudin-low subtype of triple-negative breast cancer is distinguished by its exceptionally poor prognosis, as well as a substantially higher rate of immune cell infiltration within the tumor microenvironment. Though observations suggest an inverse correlation between immune infiltration and patient prognosis in breast cancer subtypes, the link has not been confirmed.

Researchers in Jon Serody's lab at UNC Chapel Hill's Lineberger Cancer Center sought to determine how tumor-infiltrating immune cells contribute to breast tumor growth and response to immune-targeting therapies. Their work, published recently in the JCI, reports that claudin-low breast tumors contained high numbers of regulatory T cells (Tregs), a type of immune cell that suppresses immune system activity. In a mouse model of breast cancer, checkpoint inhibition therapy (an immune-targeting treatment) was unable reduce the growth of claudin-low tumors. The research determined that the increases in Tregs interfered with immune-targeting during checkpoint inhibition therapy, thus providing protecting to claudin-low tumors. Consistent with this mechanism, when Tregs were depleted, checkpoint inhibition therapy delayed claudin-low tumor growth in these mice.

These findings suggest that interfering with Treg recruitment to tumors is a potential strategy to improve targeted treatments against triple-negative breast cancer. Moreover, they support the notion that identifying the immune characteristics of breast cancer subtypes may enable more accurate and rapid application of effective therapies, which would likely improve patient outcomes.


TITLE: Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer


Jon Serody
University of North Carolina Lineberger Comprehensive Cancer Center

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