Xiang (Shawn) Zhang, PhD
Professor, Department of Molecular and Cellular Biology
Lester and Sue Smith Breast Center
Baylor College of Medicine
Identifying of factors in the tumor microenvironment that can be targeted to increase the efficacy of immunotherapy for patients with triple-negative breast cancer.
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. 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. 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. 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. 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.
Dr. Zhang and his team have categorized TNBC tumors based on the immune cells that infiltrate their TME. They identified two distinct profiles of immune cell populations—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.
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.
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