Tumor-associated macrophages expressing the transcription factor IRF8 promote T cell exhaustion in cancer.
Tumor-associated macrophages expressing the transcription factor IRF8 promote T cell exhaustion in cancer.
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表达转录因子 IRF8 的肿瘤相关巨噬细胞会促进癌症中 T 细胞的耗竭。
DOI：
10.1016/j.immuni.2022.10.002
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发表时间：
2022-11-08
期刊：
影响因子：
32.4
通讯作者：
Li, Ming O.
中科院分区：
文献类型：
--
作者：
Nixon, Briana G.;Kuo, Fengshen;Ji, LiangLiang;Liu, Ming;Capistrano, Kristelle;Do, Mytrang;Franklin, Ruth A.;Wu, Xiaodi;Kansler, Emily R.;Srivastava, Raghvendra M.;Purohit, Tanaya A.;Sanchez, Alejandro;Vuong, Lynda;Krishna, Chirag;Wang, Xinxin;Morse, Herbert C., III;Hsieh, James J.;Chan, Timothy A.;Murphy, Kenneth M.;Moon, James J.;Hakimi, A. Ari;Li, Ming O.
肿瘤由抗原提呈细胞(APC)填充，包括具有不同来源和功能的巨噬细胞亚群。在这里，我们研究了癌症如何影响乳腺癌小鼠模型中单核吞噬细胞的APC。肿瘤诱导单核细胞来源的肿瘤相关巨噬细胞(TAMs)的扩张和1型树突状细胞(DC1s)的激活，两者都表达并需要转录因子干扰素调节因子-8(IRF8)。DC1S在肿瘤引流淋巴结中介导细胞毒性T淋巴细胞(CTL)启动，而TAMS则促进肿瘤中CTL的耗竭，需要IRF8才能提呈肿瘤细胞抗原。特异性的IRF8缺失阻止了癌细胞反应性CTL的耗尽，并抑制了肿瘤的生长。免疫浸润性肾癌患者的肿瘤中有大量表达IRF8的TAMs，并富含IRF8基因表达特征。此外，-IRF8标记与CTL耗竭标记共同分离了多种癌症类型。因此，TAMS通过IRF8促进CTL耗竭。不同来源和功能的巨噬细胞存在于肿瘤中。尼克松等人。研究癌症如何影响单核细胞吞噬抗原呈递细胞，发现单核细胞来源的肿瘤相关巨噬细胞(TAMs)呈递癌细胞抗原，并驱动细胞毒性T细胞耗尽，以依赖于转录因子IRF8的方式促进肿瘤生长。
Tumors are populated by antigen presenting cells (APCs), including macrophage subsets with distinct origins and functions. Here, we examined how cancer impacts mononuclear phagocytic APCs in a murine model of breast cancer. Tumors induced expansion of monocyte-derived tumor-associated macrophages (TAMs) and activation of type 1 dendritic cells (DC1s), both of which expressed and required the transcription factor interferon regulatory factor-8 (IRF8). While DC1s mediated cytotoxic T lymphocyte (CTL) priming in tumor-draining lymph nodes, TAMs promoted CTL exhaustion in the tumor, and IRF8 was required for TAM ability to present cancer cell antigen. TAM-specific IRF8 deletion prevented exhaustion of cancer cell-reactive CTLs and suppressed tumor growth. Tumors from patients with immune-infiltrated renal cell carcinoma had abundant TAMs that expressed IRF8 and were enriched for an IRF8 gene expression signature. Furthermore, the TAM-IRF8 signature co-segregated with CTL exhaustion signatures across multiple cancer types. Thus, CTL exhaustion is promoted by TAMs via IRF8. Macrophages of distinct origin and function populate tumors. Nixon et al. examine how cancer impacts mononuclear phagocytic antigen presenting cells and find that monocyte-derived tumor-associated macrophages (TAMs) present cancer cell antigen and drive cytotoxic T cell exhaustion, promoting tumor growth in a manner dependent on the transcription factor IRF8.
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影响因子：
7.3
作者：
Dolina JS;Van Braeckel-Budimir N;Thomas GD;Salek-Ardakani S
通讯作者：
Salek-Ardakani S
DOI：
10.1158/1078-0432.ccr-08-1283
发表时间：
2009-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Beck AH;Espinosa I;Edris B;Li R;Montgomery K;Zhu S;Varma S;Marinelli RJ;van de Rijn M;West RB
通讯作者：
West RB
影响因子：
13.5
作者：
Ebrahimkhani, Mohammad R.;Mohar, Isaac;Crispe, Ian N.
通讯作者：
Crispe, Ian N.
影响因子：
20.3
作者：
Biswas, SK;Gangi, L;Sica, A
通讯作者：
Sica, A
肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franklin RA;Liao W;Sarkar A;Kim MV;Bivona MR;Liu K;Pamer EG;Li MO
通讯作者：
Li MO