Researchers have found new information regarding the changes in B cells caused by tumors in the blood and bone marrow of patients with triple-negative breast cancer. Their research reveals two specific patterns of B cell abnormalities that could potentially be used as blood biomarkers to help predict the response to standard chemotherapy and immunotherapy.
At Baylor College of Medicine and in collaboration with other institutions, researchers have unveiled fresh insights into how tumors affect B cell behavior in the blood and bone marrow of patients suffering from triple-negative breast cancer. Their findings, published in Nature Cell Biology, present two unique patterns of B cell irregularities that might serve as blood biomarkers for assessing the likelihood of responding to standard chemotherapy and immunotherapy.
“Despite considerable advancements in immunotherapy, only about 15 to 20% of patients with triple-negative breast cancer actually benefit from it,” explained Dr. Xiang H.-F. Zhang, the lead author and director of the Lester and Sue Smith Breast Center, as well as a professor of molecular and cellular biology at Baylor. “My laboratory aims to investigate why some cancers resist treatment by exploring the interactions between the tumor and the body. A range of systemic alterations occur due to the body’s response to cancer.”
Earlier research from Zhang’s lab indicated that even prior to metastasis, breast cancer can induce remote changes in immune cell development within the bone marrow. Expanding on those results, Zhang’s team looked into B cell alterations in blood samples from patients and categorized them into three subgroups. The first group, TiBA-0, showed no changes in B cells. The second group, TiBA-1, exhibited fewer B cells, likely due to competition with myeloid progenitors in the bone marrow environment. The third group, TiBA-2, demonstrated an increased count of immature B cells, possibly because a high presence of neutrophils inhibits B cell maturation. In this subgroup, immature B cells contribute to a rise in exhausted T cells.
The team discovered that the alterations in B cells within both TiBA-1 and TiBA-2 groups resulted in an immunosuppressive environment and a diminished response to treatment. Among a study of 35 patients, 78.6% of those in the TiBA-0 group achieved a complete response to chemotherapy and immunotherapy, while this figure dropped to only 33.3% for TiBA-1 and TiBA-2 patients.
“The changes in immune cells are not confined to the tumor site; they manifest systemically throughout the body, allowing us to detect these immune cell biomarkers with just a simple blood test,” noted Zhang, who also holds the William T. Butler, M.D., Endowed Chair for Distinguished Faculty and is a McNair Scholar at Baylor. He is also affiliated with the Dan L Duncan Comprehensive Cancer Center. “In the future, we could potentially categorize patients based on these biomarkers, identifying those who may not respond well to standard therapies and might need further treatment.”
The next step for Zhang’s team involves collaborating with other researchers and clinicians at the Dan L Duncan Comprehensive Cancer Center to analyze the blood biomarkers in a larger pool of patients over various points in time during treatment. His lab is also investigating methods to reverse the tumor-induced changes in bone marrow to restore the normal production of immune cells.
Additional contributors to this study include Xiaoxin Hao, Yichao Shen, Jun Liu, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L. Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G. Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T. Ueno, and Bora Lim. They are affiliated with various institutions such as Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, University of Texas MD Anderson Cancer Center, Zhejiang University, and the University of Hawai’i Cancer Center.
This research has received support from the U.S. Department of Defense, National Cancer Institute, Breast Cancer Research Foundation, McNair Medical Institute, National Institutes of Health, and the Cancer Prevention and Research Institute of Texas. For a comprehensive list of funding, refer to the publication.
