Xiang (Shawn) Zhang, PhD
Professor, Department of Molecular and Cellular Biology
William T. Butler Endowed Chair for Distinguished Faculty
Interim Director, Basic Science Research
Lester and Sue Smith Breast Center
Identifying 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 triple-negative breast cancer (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 blood cells to escape immuno-surveillance, suggesting a novel mechanism underlying therapeutic resistance to immunotherapies. In the last year, the team has focused on neutrophils specifically. They found that neutrophils work in cooperation with cancer cells for mutual survival benefit: When cancer cells differentiate and become mobile, a necessary step in tumorigenesis and metastasis, the interaction with neutrophils is altered.
In the coming year, Dr. Zhang and his team will continue to delve into the dynamic relationship between neutrophils and cancer cells that affects breast tumor progression and prevents a robust response to immunotherapy.. They will perform in-depth studies to decipher how the crosstalk between neutrophils and cancer cells influences the survival of both. In addition, Dr. Zhang and his colleagues hope to identify the types of neutrophils that participate in this crosstalk and exploit these findings to develop novel therapeutic targets to prevent it and potentially increase the efficacy of immunotherapies.
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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