Human Tumor-Infiltrating MAIT Cells Display Hallmarks of Bacterial Antigen Recognition in Colorectal Cancer.
Human Tumor-Infiltrating MAIT Cells Display Hallmarks of Bacterial Antigen Recognition in Colorectal Cancer.
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DOI：
10.1016/j.xcrm.2020.100039
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发表时间：
2020-06-23
期刊：
影响因子：
--
通讯作者：
Newell EW
中科院分区：
文献类型：
--
作者：
Li S;Simoni Y;Becht E;Loh CY;Li N;Lachance D;Koo SL;Lim TP;Tan EKW;Mathew R;Nguyen A;Golovato J;Berkson JD;Prlic M;Lee B;Minot SS;Nagarajan N;Dey N;Tan DSW;Tan IB;Newell EW
越来越多的证据表明肠道微生物群在调节人类癌症的抗肿瘤治疗功效方面发挥着作用。在这里，我们研究粘膜相关的不变T（MAIT）细胞，以寻找人类结肠癌，肺癌和肾癌中细菌抗原识别的证据。使用质谱细胞术和单细胞mRNA测序，我们鉴定了表达CD4和Foxp3的肿瘤浸润MAIT细胞亚群，并观察到仅来自结直肠癌（CRC）的MAIT细胞上CD39的高表达，我们在体外显示其在TCR刺激后特异性表达。我们进一步揭示，这些细胞的表型和功能耗尽。测序数据显示CRC肿瘤中的高细菌浸润，并突出了富集的物种，具核梭杆菌，具有以TCR依赖性方式激活MAIT细胞的能力。我们的研究结果提供了MAIT细胞对CRC中微生物抗原反应的证据，并为操纵MAIT细胞或微生物组进行癌症治疗铺平了道路。表达CD4和Foxp3的肿瘤浸润性MAIT细胞亚群的鉴定TCR驱动的CD39表达在肿瘤浸润性MAIT细胞中富集CRC相关的具核梭杆菌可以以TCR依赖性方式激活MAIT细胞。提出MAIT细胞是肠道微生物群和肿瘤生物学之间缺失的一环。这项工作将通过在微生物群影响的癌症背景下操纵MAIT细胞或MAIT相关的细菌配体来开辟癌症治疗的新途径。
Growing evidence indicates a role for the gut microbiota in modulating anti-tumor treatment efficacy in human cancer. Here we study mucosa-associated invariant T (MAIT) cells to look for evidence of bacterial antigen recognition in human colon, lung, and kidney carcinomas. Using mass cytometry and single-cell mRNA sequencing, we identify a tumor-infiltrating MAIT cell subset expressing CD4 and Foxp3 and observe high expression of CD39 on MAIT cells from colorectal cancer (CRC) only, which we show in vitro to be expressed specifically after TCR stimulation. We further reveal that these cells are phenotypically and functionally exhausted. Sequencing data show high bacterial infiltration in CRC tumors and highlight an enriched species, Fusobacteria nucleatum, with capability to activate MAIT cells in a TCR-dependent way. Our results provide evidence of a MAIT cell response to microbial antigens in CRC and could pave the way for manipulating MAIT cells or the microbiome for cancer therapy. Comprehensive profiling of tumor-infiltrating MAIT cells in colorectal cancer (CRC) Identification of a tumor-infiltrating MAIT cell subset expressing CD4 and Foxp3 TCR-driven CD39 expression is enriched in tumor-infiltrating MAIT cells CRC-related Fusobacterium nucleatum can activate MAIT cells in a TCR-dependent way By investigating human colon, lung, and kidney carcinomas, Li et al. propose MAIT cells as part of the missing link between the gut microbiota and tumor biology. This work will open new avenues in cancer therapy by manipulating MAIT cells or MAIT-related bacterial ligands in the context of microbiota-influenced cancers.
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影响因子：
8
作者：
Gibbs A;Leeansyah E;Introini A;Paquin-Proulx D;Hasselrot K;Andersson E;Broliden K;Sandberg JK;Tjernlund A
通讯作者：
Tjernlund A
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
DOI：
10.1126/science.aax6624
发表时间：
2019-10-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Constantinides MG;Link VM;Tamoutounour S;Wong AC;Perez-Chaparro PJ;Han SJ;Chen YE;Li K;Farhat S;Weckel A;Krishnamurthy SR;Vujkovic-Cvijin I;Linehan JL;Bouladoux N;Merrill ED;Roy S;Cua DJ;Adams EJ;Bhandoola A;Scharschmidt TC;Aubé J;Fischbach MA;Belkaid Y
通讯作者：
Belkaid Y
影响因子：
7
作者：
Castellarin, Mauro;Warren, Rene L.;Holt, Robert A.
通讯作者：
Holt, Robert A.