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Xiang (Shawn) Zhang, PhD
Professor, Department of Molecular and Cellular Biology
Lester and Sue Smith Breast Center
Baylor College of Medicine
Goal: To identify factors that mediate the interaction of tumor cells and the tumor microenvironment in response to immunotherapy in triple-negative breast cancer patients.
Impact: Dr. Zhang is conducting laboratory studies to understand how the interaction of immune cells in and around the tumor affect tumor progression and response to treatment. The results of his studies will provide insight into the response of triple-negative breast cancer (TNBC) patients to immunotherapies such as anti PD-L1 checkpoint inhibitors, as well as possible resistance mechanisms that may arise during the treatment.
What’s next: Dr. Zhang and his team have identified two distinct immune profiles in TNBC and will continue to characterize these subtypes to determine their role in the response to immune checkpoint blockade therapy.
The microenvironment surrounding breast tumors contains a variety of non-tumor cells including multiple kinds of immune cells. These immune cells may play opposite roles: some will fight against tumors, but others enable tumor cells to evade immune surveillance. Dr. Zhang is delineating the different types of immune cell populations in the microenvironment of TNBC tumors and determining how they affect breast tumor progression and decrease the efficacy of immunotherapy.
Full Research Summary
Research area: Identification of factors in the tumor microenvironment that can be targeted to increase the efficacy of immunotherapy for patients with triple-negative breast cancer.
Impact: Immunotherapies including immune checkpoint blockade (ICB) with anti-PD-L1 inhibitors have revolutionized treatment of several cancer types. However, the majority of breast cancer patients have not benefited from this progress. Previous research shows that one of the major barriers to effective ICB therapy is the presence of tumor-promoting immune cells in the tumor microenvironment (TME). Importantly, the exact type and nature of these immune cells vary from patient to patient. In this project, Dr. Zhang will investigate how individual breast tumors evolve to enrich specific types of tumor-promoting immune cells. His team will determine methods to precisely identify and block the functions of these cells. Through these investigations, they hope to increase the number of breast cancer patients that can benefit from ICB and other immunotherapies and to extend the concept of precision medicine to include targetable factors in the TME as well.
Current investigation: Dr. Zhang and his colleagues are conducting studies to identify genes and molecules that mediate the communication between cancer cells and immune cells to promote tumor growth and expansion. By interrupting this crosstalk, they hope to enhance the efficacy of immune checkpoint blockade therapy.
What he’s learned so far: Dr. Zhang and his team have categorized triple-negative breast cancer (TNBC) tumors based on the immune cells that infiltrate their TME. They identified two distinct profiles of immune cell populations which exhibited a wide diversity in numbers and qualities across patients—a neutrophil-enriched subtype (NES) and a macrophage-enriched subtype (MES). NES and MES tumors appear to rely on different types of myeloid (blood) cells to escape immunosurveillance suggesting a novel mechanism underlying therapeutic resistance to immunotherapies.
What’s next: In the coming year, -Dr. Zhang and his team will delve into determining how macrophages and neutrophils affect breast tumor progression and prevent a robust response to immunotherapy with checkpoint blockade agents. Utilizing various laboratory models, they will identify genes and molecules that mediate the crosstalk between cancer cells and these immune cells. They will also determine ways to disrupt this crosstalk to enhance immune checkpoint blockade therapy and increase the proportion of patients that may benefit from this treatment.
Dr. Zhang is an Associate tenured Professor at Lester and Sue Smith Breast Center of Baylor College of Medicine. 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. He made several findings using an integrative strategy combining cancer genomics and experimental metastasis approaches. He was named McNair Scholar in 2011. He is also an awardee of the K99/R00 Pathways to Independence Grant from National Cancer Institute. At Baylor College of Medicine, Dr. Zhang continues to investigate biological mechanisms and therapeutic strategies of breast cancer metastasis. His long-term goals are to eradicate latent cancer cells in distant organs, and to reduce the incidence of overt-metastases.