posted on 2025-01-09, 08:22authored byYu Zhang, Yangyang Li, Zhengfeng Zhang, Xiaodong Zheng, Hui Peng, Zhigang Tian, Rui Sun, Haoyu Sun
CD49a deficiency in NK cells does not affect NK cells maturation.
Funding
National Key Research and Development Program of China (NKPs)
National Natural Science Foundation of China (NSFC)
Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM
History
ARTICLE ABSTRACT
Approximately 70% of patients receiving immune checkpoint blockade therapies develop treatment resistance. Thus, there is a need for the identification of additional immunotherapeutic targets. CD49a is a membrane protein expressed on NK cells and T cells. In this study, we found that CD49a was highly expressed on the surface of tumor-infiltrating NK cells in various mouse tumor models and that CD49a+ tumor-infiltrating NK cells were more exhausted than CD49a− tumor-infiltrating NK cells. Furthermore, CD49a or NK-specific CD49a deficiency slowed tumor growth and prolonged survival in several mouse tumor models, primarily through the essential role played by NK cells in antitumor activities. Blockade of CD49a using an mAb suppressed tumor development in mice, and combination treatment with anti–PD-L1 further enhanced antitumor efficacy. Our research reveals CD49a on NK cells as an immunotherapeutic target and highlights the potential clinical applications of CD49a-targeted therapies.