Tumor-induced B cell alterations reveal a potential biomarker of treatment response in triple-negative breast cancer

Researchers from Baylor College of Medicine and collaborating institutions have uncovered new insights into tumor-induced B cell changes in the blood and bone marrow of patients with triple-negative breast cancer. The findings, published in Natural Cell Biologyshow two distinct patterns of B cell abnormalities that could serve as blood biomarkers to determine the likelihood of response to standard chemotherapy and immunotherapy.

“Even with significant advances in immunotherapy, only 15 to 20 percent of patients with triple-negative breast cancer will benefit from this treatment,” said corresponding author Xiang H.-F. Zhang, MD, director of the Lester and Sue Smith Breast Center and professor of molecular and cellular biology at Baylor.

“My lab is trying to understand why some cancers don’t respond to treatment by looking at the interactions between the tumor and the body. Many systemic changes occur because of how the body responds to cancer.”

A previous study from Zhang’s lab showed that even before tumor metastasis, breast cancer induces distant changes in immune cell development in the bone marrow. Building on these findings, Zhang’s team looked at changes in B cells from patient blood samples and identified three subgroups.

The first group, TiBA-0, shows no changes in B cells. The second group, TiBA-1, shows reduced numbers of B cells, likely due to competition with myeloid progenitors in the bone marrow microenvironment. The third group, TiBA-2, shows increased numbers of immature B cells, likely due to excessive neutrophils preventing B cells from maturing. In this group, immature B cells lead to an increase in exhausted T cells.

Researchers found that changes in TiBA-1 and TiBA-2 B cells lead to an immunosuppressive effect and poorer response to treatment. In a study of 35 patients, 78.6% of TiBA-0 patients had a complete response to chemotherapy and immunotherapy, while only 33.3% of TiBA-1 and TiBA-2 patients had a complete response.

“These immune cell changes don’t just happen locally within the tumor. We see them systemically throughout the body, which means we can identify these immune cell biomarkers with a simple blood draw,” said Zhang, the William T. Butler, MD, Distinguished Professorship and McNair Scholar at Baylor. He is also a member of the Dan L Duncan Comprehensive Cancer Center.

“In the future, we may be able to stratify patients based on these biomarkers and determine which patients are less likely to respond to standard therapies and require additional treatment.”

Zhang’s team will then work with other researchers and clinicians at the Dan L Duncan Comprehensive Cancer Center to study blood biomarkers in a larger group of patients at multiple time points during treatment to learn more about how immune cells may change over time. His lab is also studying ways to reverse tumor-induced changes in the bone marrow to restore normal immune cell production.