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B and T Immune Cells: A Biomarker of Response to Immunotherapy for Breast Cancer?

By: Melissa E. Fryman, MS
Posted: Friday, January 31, 2020

The coordination of B cells and T follicular helper cells seems essential in mediating immune checkpoint inhibitor treatment responses in some breast cancers, according to Charles M. Perou, PhD, and colleagues, of the University of North Carolina Lineberger Comprehensive Cancer Center. Results from their study, published in Cell, indicate that lack of this coordination by the adaptive immune system may be one reason some cancers do not respond to immunotherapy.

“Potentially, we have a new biomarker to be used to figure out which triple-negative breast cancer patients should be receiving immunotherapies,” said Dr. Perou in a press release from the University of North Carolina Health Care System.

In this study, the researchers first developed triple-negative breast cancer mouse models with a high tumor burden, consistent with that in other tumors that respond to immune checkpoint inhibitor therapy. The mice were treated with anti–PD-1 and anti–CTLA-4 therapies, and researchers then used mRNA sequencing to compare the expression signatures of tumors that responded and those that did not. They also analyzed the published data sets from six clinical trials of patients with melanoma and breast cancer, to determine whether this expression signature was also present in the cancers of responders.

Compared with nonmutagenized mouse models of breast cancer, those induced to have a high tumor burden showed a robust response to immune checkpoint inhibitor therapy, as well as a significant elevation of a B-cell/T-cell co-cluster. Moreover, this co-cluster was also seen in the data sets from tumors belonging to patients who responded to therapy.

“Our work going forward is to look for ways to leverage B cells to improve treatment plans and regimens for breast cancer patients,” concluded first author Daniel P. Hollern, PhD. “We definitely need to be looking at ways to activate B cells more effectively with our therapies.”

Disclosure: The full disclosures of the study authors can be found at cell.com.



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