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Figure S6 from CD49a Targeting Enhances NK Cell Function and Antitumor Immunity

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posted on 2025-01-09, 08:22 authored by Yu Zhang, Yangyang Li, Zhengfeng Zhang, Xiaodong Zheng, Hui Peng, Zhigang Tian, Rui Sun, Haoyu Sun

Inducible CD49a knockout in NK cells prevents tumor growth and prolongs survival in experimental lung metastasis model.

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

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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.

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