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Can B Cells Determine Immunotherapy Responses in Advanced Melanoma?

By: Cordi Craig
Posted: Thursday, January 30, 2020

According to a study published in Nature, the probability of a patient’s response to immune checkpoint blockade therapy may depend on B cells and tertiary lymphoid structures, both located within the tumor. Among patients with melanoma, the researchers found that B-cell markers seemed to be the most differentially expressed genes in tumors of patients who responded to treatment versus those who did not respond.

“These findings open up a whole new area―that B cells are actually big drivers in cancer immunotherapy, specifically, checkpoint blockade,” said Jennifer A. Wargo, MD, of The University of Texas MD Anderson Cancer, Houston, in a press release. “This could lead us to important biomarkers for therapy response as well as potentially new therapeutic options.”

Using bulk RNA sequencing, the research team examined tumor samples from patients with advanced melanoma who were receiving neoadjuvant checkpoint inhibitors. Samples were collected at baseline and during treatment.

The expression of B-cell–related genes was significantly higher in responders than in nonresponders (P < .001). Additionally, the expression of B-cell–related genes was predictive of response to checkpoint blockade (P = .02). The researchers found that B cells were localized in the tertiary lymphoid structures of the tumor. A higher density of B cells and tertiary lymphoid structures was found in responders than in nonresponders.

“Although the distinct mechanisms through which B cells contribute are incompletely understood, our data suggest that the same properties of memory B cells and plasma cells desirable for acquired immune responses may also be contributing to an effective T-cell response after immune checkpoint blockade,” the authors concluded.

Disclosure: For full disclosures of the study authors, visit nature.com.



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