CD49a targeting enhances NK cell function and antitumor immunity.

IF 8.1 1区 医学 Q1 IMMUNOLOGY
Yu Zhang, Yangyang Li, Zhengfeng Zhang, Xiaodong Zheng, Hui Peng, Zhigang Tian, Rui Sun, Haoyu Sun
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引用次数: 0

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 a monoclonal antibody 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.

CD49a 靶向可增强 NK 细胞功能和抗肿瘤免疫力。
在接受免疫检查点阻断疗法的患者中,约有 70% 会产生耐药性。因此,需要确定更多的免疫治疗靶点。CD49a 是一种在 NK 细胞和 T 细胞上表达的膜蛋白。本研究发现,在各种小鼠肿瘤模型中,CD49a在肿瘤浸润NK细胞表面高表达,CD49a+肿瘤浸润NK细胞比CD49a-肿瘤浸润NK细胞更衰竭。此外,在几种小鼠肿瘤模型中,CD49a或NK特异性CD49a缺乏可减缓肿瘤生长并延长存活时间,这主要是由于NK细胞在抗肿瘤活动中发挥了重要作用。使用单克隆抗体阻断CD49a可抑制小鼠的肿瘤发生,与抗PD-L1联合治疗可进一步提高抗肿瘤疗效。我们的研究揭示了NK细胞上的CD49a是一个免疫治疗靶点,并强调了CD49a靶向疗法的潜在临床应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer immunology research
Cancer immunology research ONCOLOGY-IMMUNOLOGY
CiteScore
15.60
自引率
1.00%
发文量
260
期刊介绍: Cancer Immunology Research publishes exceptional original articles showcasing significant breakthroughs across the spectrum of cancer immunology. From fundamental inquiries into host-tumor interactions to developmental therapeutics, early translational studies, and comprehensive analyses of late-stage clinical trials, the journal provides a comprehensive view of the discipline. In addition to original research, the journal features reviews and opinion pieces of broad significance, fostering cross-disciplinary collaboration within the cancer research community. Serving as a premier resource for immunology knowledge in cancer research, the journal drives deeper insights into the host-tumor relationship, potent cancer treatments, and enhanced clinical outcomes. Key areas of interest include endogenous antitumor immunity, tumor-promoting inflammation, cancer antigens, vaccines, antibodies, cellular therapy, cytokines, immune regulation, immune suppression, immunomodulatory effects of cancer treatment, emerging technologies, and insightful clinical investigations with immunological implications.
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