MAIT cells regulate NK cell-mediated tumor immunity.
MAIT cells regulate NK cell-mediated tumor immunity.
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DOI：
10.1038/s41467-021-25009-4
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发表时间：
2021-08-06
影响因子：
16.6
通讯作者：
Darcy PK
中科院分区：
文献类型：
--
作者：
Petley EV;Koay HF;Henderson MA;Sek K;Todd KL;Keam SP;Lai J;House IG;Li J;Zethoven M;Chen AXY;Oliver AJ;Michie J;Freeman AJ;Giuffrida L;Chan JD;Pizzolla A;Mak JYW;McCulloch TR;Souza-Fonseca-Guimaraes F;Kearney CJ;Millen R;Ramsay RG;Huntington ND;McCluskey J;Oliaro J;Fairlie DP;Neeson PJ;Godfrey DI;Beavis PA;Darcy PK
MR1限制性粘膜相关不变T细胞(MAIT)在肿瘤免疫中的作用尚不清楚。在这里，我们表明MAIT细胞缺陷小鼠与对照小鼠相比，增强了对转移性B16F10肿瘤生长的NK细胞依赖的控制。对人类肿瘤样本中这种相互作用的分析表明，MAIT细胞基因信号的高表达对NK细胞的预后意义产生负面影响。矛盾的是，用MAIT细胞抗原预先冲击肿瘤，或在体内激活MAIT细胞，在B16F10和E0771小鼠肿瘤模型中增强抗肿瘤免疫，包括在已建立的转移的背景下。这些效应与增强的NK细胞反应和NK细胞中干扰素-γ依赖基因和炎症基因的表达增加有关。重要的是，激活的人MAIT细胞也促进了从患者肿瘤样本中分离的NK细胞的功能。因此，我们的结果描述了NK细胞的激活依赖、MAIT和细胞介导的调节，并为癌症治疗提供了一条潜在的治疗途径。粘膜相关不变T细胞(MAIT)有助于抗微生物反应，但其在癌症保护中的功能尚不清楚。在这里，作者发现激活的MAIT细胞诱导自然杀伤(NK)细胞中的干扰素-γ转录组，并增强自然杀伤(NK)依赖的小鼠的抗癌免疫，从而暗示了一种新的癌症治疗途径。
The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment. Mucosal-associated invariant T (MAIT) cells facilitate anti-microbial responses, but their functions in cancer protection is unclear. Here the authors show that activated MAIT cells induce an IFN-γ transcriptome in natural killer (NK) cells and enhance NK-dependent anti-cancer immunity in mice, thereby hinting a new avenue for cancer therapy.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
15.9
作者：
Cui, Yue;Franciszkiewicz, Katarzyna;Lantz, Olivier
通讯作者：
Lantz, Olivier
影响因子：
9.8
作者：
Gold MC;Cerri S;Smyk-Pearson S;Cansler ME;Vogt TM;Delepine J;Winata E;Swarbrick GM;Chua WJ;Yu YY;Lantz O;Cook MS;Null MD;Jacoby DB;Harriff MJ;Lewinsohn DA;Hansen TH;Lewinsohn DM
通讯作者：
Lewinsohn DM
DOI：
10.1084/jem.20140484
发表时间：
2014-07-28
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Eckle SB;Birkinshaw RW;Kostenko L;Corbett AJ;McWilliam HE;Reantragoon R;Chen Z;Gherardin NA;Beddoe T;Liu L;Patel O;Meehan B;Fairlie DP;Villadangos JA;Godfrey DI;Kjer-Nielsen L;McCluskey J;Rossjohn J
通讯作者：
Rossjohn J
影响因子：
30.5
作者：
Crowther, Michael D.;Dotlon, Garry;Sewell, Andrew K.
通讯作者：
Sewell, Andrew K.