A subpopulation of CD146(+) macrophages enhances antitumor immunity by activating the NLRP3 inflammasome.
A subpopulation of CD146(+) macrophages enhances antitumor immunity by activating the NLRP3 inflammasome.
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DOI：
10.1038/s41423-023-01047-4
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发表时间：
2023-08
影响因子：
24.1
通讯作者：
中科院分区：
文献类型：
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作者：
肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs）作为肿瘤浸润的主要免疫细胞类型之一，决定着免疫治疗的疗效。然而，有限的知识，其表型和功能异质性的性质限制了它们在肿瘤免疫治疗中的应用。在这项研究中，我们确定了一个亚群的CD 146 + TAMs，发挥抗肿瘤活性，在人类样本和动物模型。TAM中的CD 146表达受STAT 3信号传导负控制。减少这一群体的TAM促进肿瘤的发展，促进骨髓来源的抑制细胞通过激活JNK信号的招聘。有趣的是，CD 146参与肿瘤微环境中NLRP 3炎性小体介导的巨噬细胞活化，部分通过抑制跨膜蛋白176 B（TMEM 176 B），一种免疫调节阳离子通道。用TMEM 176 B抑制剂处理增强了CD 146 + TAM的抗肿瘤活性。这些数据揭示了CD 146 + TAM的关键抗肿瘤作用，并突出了抑制CD 146和TMEM 176 B的有前景的免疫学方法。
As one of the main tumor-infiltrating immune cell types, tumor-associated macrophages (TAMs) determine the efficacy of immunotherapy. However, limited knowledge about their phenotypically and functionally heterogeneous nature restricts their application in tumor immunotherapy. In this study, we identified a subpopulation of CD146+ TAMs that exerted antitumor activity in both human samples and animal models. CD146 expression in TAMs was negatively controlled by STAT3 signaling. Reducing this population of TAMs promoted tumor development by facilitating myeloid-derived suppressor cell recruitment via activation of JNK signaling. Interestingly, CD146 was involved in the NLRP3 inflammasome-mediated activation of macrophages in the tumor microenvironment, partially by inhibiting transmembrane protein 176B (TMEM176B), an immunoregulatory cation channel. Treatment with a TMEM176B inhibitor enhanced the antitumor activity of CD146+ TAMs. These data reveal a crucial antitumor role of CD146+ TAMs and highlight the promising immunotherapeutic approach of inhibiting CD146 and TMEM176B.
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巨噬细胞 CD146 促进动脉粥样硬化期间泡沫细胞的形成和保留
影响因子：
44.1
作者：
Luo Y;Duan H;Qian Y;Feng L;Wu Z;Wang F;Feng J;Yang D;Qin Z;Yan X
通讯作者：
Yan X
影响因子：
64.8
作者：
De Henau O;Rausch M;Winkler D;Campesato LF;Liu C;Cymerman DH;Budhu S;Ghosh A;Pink M;Tchaicha J;Douglas M;Tibbitts T;Sharma S;Proctor J;Kosmider N;White K;Stern H;Soglia J;Adams J;Palombella VJ;McGovern K;Kutok JL;Wolchok JD;Merghoub T
通讯作者：
Merghoub T
影响因子：
7.3
作者：
Pan Y;Yu Y;Wang X;Zhang T
通讯作者：
Zhang T
DOI：
10.1038/nrclinonc.2016.217
发表时间：
2017-07
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Mantovani A;Marchesi F;Malesci A;Laghi L;Allavena P
通讯作者：
Allavena P
影响因子：
5.2
作者：
Cendrowicz E;Sas Z;Bremer E;Rygiel TP
通讯作者：
Rygiel TP