When French cancer genomics researcher Florent Petitprez, PhD, wanted to understand why some patients with soft-tissue sarcoma survived longer than others, he expected the answer to come down to which individuals had the most T cells — which are the well-studied cells known to contribute to immunotherapy success. Yet when he studied the gene expression of 608 tumors across subtypes of the disease in a paper recently published in Nature, he noticed a surprising trend: The patients with the best prognoses had a stronger signature for B cells located within specialized immune-cell clusters, called tertiary lymphoid structures, found at tumor sites.1 That group of patients also had a high response rate to PD-1 blockade with pembrolizumab in a phase 2 clinical trial.2
“Usually in this field most people are focusing on T cells because they’re the immune cells that are mostly responsible for targeting and killing tumor cells,” said Dr Petitprez, who conducted the research at the French National Institute of Health and Medical Research and the French League Against Cancer in Paris. (He currently works at the latter.) “But our work is important because we showed that B cells contribute to immune checkpoint blockade response. This could be a good tool to guide therapeutic decisions so patients get treatment that’s most likely to be effective for their particular cancer.”
Dr Petitprez’s work is 1 of a trio of papers published earlier this year in Nature that make the case that B cells deserve more research attention for their role in boosting antitumor immunity across several kinds of cancer, including melanoma and renal cell carcinoma (RCC). Although the exact mechanism of action is still unknown, the ability of B cells to generate antibodies suggests they serve as a boost to T cells, and play a dynamic role among several components of the immune system.
“We’ve been focused for so many years on T cells and how they would predict who responds to immunotherapy, but we realize there are other cell types involved in immune response,” said corresponding author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology at the University of Texas MD Anderson Cancer Center in Houston. One of the other Nature studies conducted by a Swedish team at Lund University found that both T cells and B cells were associated with improved survival in patients with metastatic melanoma.3
Dr Wargo and her colleagues had previously shown that giving immunotherapy to patients with high-risk resectable metastatic melanoma before surgery was associated with a high rate of success. They noticed that individuals who had the best responses consistently had strong B-cell signatures. “We dug deeper and came to realize this wasn’t a fluke or a finding from our group only. We were seeing this in multiple cohorts across multiple cancer types across the world,” she said. “There’s a big opportunity to study B cells along with other biomarkers to see how they might predict how cancer patients will respond to therapy.”