ω-3多不饱和脂肪酸二十二碳六烯酸能增强NK细胞的抗肿瘤效应功能。

IF 8.1 1区 医学 Q1 IMMUNOLOGY
Shuting Wu, Hongyan Peng, Songyang Li, Lanlan Huang, Xiangyu Wang, Yana Li, Yongjie Liu, Peiwen Xiong, Qinglan Yang, Kunpeng Tian, Weiru Wu, Rongxi Pu, Xiulan Lu, Zhenghui Xiao, Jian Yang, Zhaoyang Zhong, Yuan Gao, Yafei Deng, Youcai Deng
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引用次数: 0

摘要

众所周知,ω-3 多不饱和脂肪酸(PUFA)可直接抑制肿瘤的发展和恶化。在这项研究中,我们探讨了二十二碳六烯酸(DHA)(一种ω-3多不饱和脂肪酸)在促进免疫功能正常的小鼠肿瘤生长方面是否具有免疫调节作用。在生理条件下,各种组织中补充 DHA 会减少自然杀伤细胞(NK)的数量,但不会减少 T 细胞或 B 细胞的数量。在小鼠 B16F10 黑色素瘤模型中,虽然 NK 细胞的频率和数量相当,但补充 DHA 的小鼠脾脏和肺部的 NK 细胞产生的 IFN-γ 均有所增加。单细胞 RNA 测序(scRNA-seq)显示,DHA 促进了 NK 细胞的效应功能和氧化磷酸化,但对其他免疫细胞没有明显影响。利用Rag2-/-小鼠和通过注射PK136抗体消耗NK细胞,我们证明了补充DHA对肺部B16F10黑色素瘤生长的抑制主要依赖于NK细胞。体外实验表明,DHA能直接增强NK细胞中IFN-γ的产生、CD107a的表达和线粒体氧化磷酸化(OXPHOS)活性,并能轻微增加增殖体激活受体γ辅激活剂-1α(PGC-1α)蛋白的表达。体外 PGC-1α 抑制剂 SR-18292 和小鼠 NK 细胞特异性 PGC-1α 基因敲除可逆转 DHA 的抗肿瘤作用。总之,我们的研究结果从免疫调节的角度拓宽了目前关于补充 DHA 如何通过上调 NK 细胞中 PGC-1α 信号介导的线粒体 OXPHOS 活性来保护癌症生长的知识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The ω-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid Enhances NK-Cell Antitumor Effector Functions.

ω-3 polyunsaturated fatty acids (PUFA) are known to directly repress tumor development and progression. In this study, we explored whether docosahexaenoic acid (DHA), a type of ω-3 PUFA, had an immunomodulatory role in inhibiting tumor growth in immunocompetent mice. The number of natural killer (NK) cells but not the number of T or B cells was decreased by DHA supplementation in various tissues under physiologic conditions. Although the frequency and number of NK cells were comparable, IFNγ production by NK cells in both the spleen and lung was increased in DHA-supplemented mice in the mouse B16F10 melanoma tumor model. Single-cell RNA sequencing revealed that DHA promoted effector function and oxidative phosphorylation in NK cells but had no obvious effects on other immune cells. Using Rag2-/- mice and NK-cell depletion by PK136 antibody injection, we demonstrated that the suppression of B16F10 melanoma tumor growth in the lung by DHA supplementation was dependent mainly on NK cells. In vitro experiments showed that DHA directly enhanced IFNγ production, CD107a expression, and mitochondrial oxidative phosphorylation (OXPHOS) activity and slightly increased proliferator-activated receptor gamma coactivator-1α (PGC-1α) protein expression in NK cells. The PGC-1α inhibitor SR-18292 in vitro and NK cell-specific knockout of PGC-1α in mice reversed the antitumor effects of DHA. In summary, our findings broaden the current knowledge on how DHA supplementation protects against cancer growth from the perspective of immunomodulation by upregulating PGC-1α signaling-mediated mitochondrial OXPHOS activity in NK cells.

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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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