Titles and Affiliations
Professor, Department of Molecular and Cellular Biology
William T. Butler Endowed Chair for Distinguished Faculty
Director, Basic Science Research
Lester and Sue Smith Breast Center
Research area
Investigating ways to enhance the efficacy of immunotherapies in breast cancer.
Impact
Some breast tumors can evade the immune system, develop resistance to therapy, and metastasize. They accomplish this by directly influencing specific cells of the immune system, even those that are far from the tumor itself. One of these immune cells, B-cells, are profoundly altered to the point where they are dysfunctional and cannot participate in a robust immune response to breast tumors. Dr. Zhang is examining breast tumor-induced B cell dysfunctions which are diverse across the patient population. His team identified several forms of tumor-induced B cell abnormality, in patients with triple-negative breast cancer (TNBC) and in laboratory models of TNBC. Dr. Zhang and his colleagues are exploring B-cell abnormality to potentially uncover biomarkers and therapeutic targets that can be used to predict outcomes of immunotherapy or overcome immunosuppression, particularly in aggressive breast cancers such as TNBC.
Progress Thus Far
Dr. Zhang and his team classified tumor-induced B cell abnormality into three categories from 0 to 2 based on their effect on B-cell production and function. Type 0 shows no characteristic difference from a normal B-cell population; Type 1 abnormality exhibits a global reduction in B cells; Type 2 has an accumulation of immature B cells, which may be immunosuppressive; The team is utilizing cutting-edge single-cell technology to characterize the abnormal B cells and validate their functions in laboratory models. Clinical analysis showed that patients with TNBC and TiBA-1 or TiBA-2 immune signatures had significantly lower rates of pathological complete response (pCR) following neoadjuvant chemo-immunotherapy compared to patients without these abnormalities. These findings indicate that peripheral blood profiling of myeloid and B cell populations could serve as a predictive tool for treatment responses.
What’s next
Dr. Zhang’s team will continue a comprehensive molecular characterization of the immune cells in different pre-clinical models and investigate how the same lineage of immune cells can be systemically altered in divergent directions to become immunosuppressive. Specifically, they will investigate the tumor-derived factors responsible for the development of TiBA-1 and TiBA-2 immune behaviors. And they will explore how standard-of-care therapies, particularly chemotherapy and immunotherapy, impact tumor-induced systemic immune alterations. Together, their results will provide critical insights into the mechanisms of tumor-induced systemic immunosuppression and establish a strong rationale for developing blood-based biomarkers to guide treatment decisions and overcome therapeutic resistance in TNBC.
Biography
Xiang (Shawn) Zhang, PhD is a Professor in the Department of Molecular and Cellular Biology, the William T. Butler Endowed Chair for Distinguished Faculty, and the Interim Director of Basic Research at the Lester and Sue Smith Breast Center of Baylor College of Medicine in Houston, Texas. Dr. Zhang continues to investigate biological mechanisms and therapeutic strategies of breast cancer metastasis and has made several findings using an integrative strategy that combines cancer genomics and experimental metastasis approaches. His long-term goals are to eradicate latent cancer cells in distant organs, and to reduce the incidence of overt metastases.
He received his PhD degree from Columbia University under the mentorship of Dr. Lawrence Chasin where he focused on the biology of mRNA splicing. He then joined Dr. Joan Massague’s laboratory at Memorial Sloan Kettering Cancer Center, where he began to study cancer metastasis.
Dr. Zhang is the recipient of several prestigious awards: Laura Ziskin Translational Research Award of Breast Cancer (2022), Michael E. DeBakey Excellence in Research Award, Baylor College of Medicine (2018), Sue Eccles Young Investigator Award, Metastasis Research Society (2018), Leadership Award, Teresa Research Foundation (2016), Excellence in Research Award, Baylor College of Medicine (2016), Era of Hope Scholar Award, Department of Defense, Breast Cancer Research Program (2015), Career Catalyst Research Award, Susan G. Komen Foundation (2015). He is also an awardee of the K99/R00 Pathways to Independence Grant from the National Cancer Institute.
“If not for BCRF, our high-risk research uncovering how tumors reshape immunity would not exist. Their brave support drives discoveries that bring new hope to breast cancer patients.”
