A new pre-clinical study by researchers at Winship Cancer Institute of Emory University and published in Science Advances suggests promising new strategies to improve the efficacy of immunotherapy in patients with triple negative breast cancer. In comparison to other types of breast cancer, triple negative breast cancer tends to grow and spread faster, and it has fewer treatment options and worse outcomes.
Conducted by the lab of Yong Wan, PhD, a member of Winship's Cell and Molecular Biology Research Program and director for basic research at Winship's Glenn Family Breast Center, the study points to CD73, a protein that plays a key role in tumor growth and metastasis, as a potential therapeutic target for treating triple negative breast cancer.
"This study uncovered the mystery of CD73 in breast cancer tumors that do not trigger a strong immune response, including how the CD73 abundance is controlled and how the deregulated CD73 expression contributes to the immune escape in triple negative breast cancer," says Wan, who is also the SOM Endowed Professor in the Department of Pharmacology and Chemical Biology at Emory University School of Medicine.
|Yong Wan, PhD|
Wan explains that the study's findings uncover a novel mechanism that governs the breakdown of CD73 and point to a potentially new treatment strategy that modulates that breakdown. The enzyme that facilitates the breakdown, known as TRIM21, was found to restore effector T cells—the key players in steering immune responses to execute immune functions. The study found that a high level of TRIM21 and low level of CD73 in a subgroup of human breast malignancies is associated with a favorable immune profile.
In future research, Wan and his team plan to develop small molecules that target CD73 through its regulation of the chemical changes in the protein, known as posttranslational modifications.
Additional researchers from the Wan lab who contributed to the study are cancer biologist Yueming Zhu, PhD, a member of Winship's Cell and Molecular Biology Research Program and assistant professor of pharmacology and chemical biology at the Emory University School of Medicine; Donghong Zhang, PhD, an instructor of pharmacology and chemical biology; Jiao Qiao, a master's student specializing in cancer biology and translational oncology at Emory University’s Laney Graduate School; Junlong Chi, a PhD student in pharmacology and chemical biology at the Laney Graduate School; and Kevin Kalinsky, MD, MS, director of breast medical oncology at Winship, director of Winship’s Glenn Family Breast Center, associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine and the Louisa and Rand Glenn Family Chair in Breast Cancer Research.
This work was partially supported by NIH R01CA258857, NIH R01CA258765, NIH R01CA250110 and NIH R01CA202948.