Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer.
Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer.
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肿瘤浸润 T 辅助细胞 17 在人类结直肠癌中的双重作用。
DOI：
10.1136/gutjnl-2015-310016
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发表时间：
2017-04
期刊：
影响因子：
24.5
通讯作者：
Iezzi G
中科院分区：
文献类型：
--
作者：
Amicarella F;Muraro MG;Hirt C;Cremonesi E;Padovan E;Mele V;Governa V;Han J;Huber X;Droeser RA;Zuber M;Adamina M;Bolli M;Rosso R;Lugli A;Zlobec I;Terracciano L;Tornillo L;Zajac P;Eppenberger-Castori S;Trapani F;Oertli D;Iezzi G
免疫环境预测人类结直肠癌的预后。虽然肿瘤浸润性CD8+T细胞和髓系CD16+髓过氧化物酶(MPO)+细胞与良好的临床预后相关，但产生白细胞介素17的细胞被报道与严重的预后相关。然而，它们的表型和功能仍然存在争议。探讨结直肠癌浸润性IL-17细胞的临床相关性、表型和功能特征。采用免疫组织化学方法对1148例癌组织芯片进行IL-17染色。用流式细胞仪对临床标本的酶消化细胞悬液进行IL-17产生细胞表型的检测。通过体外和体内实验评估CRC分离的产生IL-17的细胞的功能。IL-17+浸润物本身并不预示不良的临床结果，但与CD8+T细胞和CD16+MPO+中性粒细胞的浸润性相关。体外分析表明，肿瘤浸润性IL-17+细胞主要由具有多方面特性的CD4+T辅助细胞(Th17)组成。事实上，由于IL-17的分泌，CRC来源的Th17通过肿瘤和肿瘤相关的间质触发了促肿瘤因子的释放。然而，另一方面，他们倾向于通过分泌IL-8来招募有益的中性粒细胞，最重要的是，他们通过CCL5和CCL20的释放，推动高度细胞毒性的CCR5+CCR6+CD8+T细胞进入肿瘤组织。与这些发现一致的是，上皮内Th17细胞的存在，而不是间质Th17细胞的存在，与存活率的提高呈正相关。我们的研究显示了肿瘤浸润性Th17在结直肠癌中所起的双重作用，因此建议在开发新的IL-17/Th17靶向治疗时要谨慎。
The immune contexture predicts prognosis in human colorectal cancer (CRC). Whereas tumour-infiltrating CD8+ T cells and myeloid CD16+ myeloperoxidase (MPO)+ cells are associated with favourable clinical outcome, interleukin (IL)-17-producing cells have been reported to correlate with severe prognosis. However, their phenotypes and functions continue to be debated. To investigate clinical relevance, phenotypes and functional features of CRC-infiltrating, IL-17-producing cells. IL-17 staining was performed by immunohistochemistry on a tissue microarray including 1148 CRCs. Phenotypes of IL-17-producing cells were evaluated by flow cytometry on cell suspensions obtained by enzymatic digestion of clinical specimens. Functions of CRC-isolated, IL-17-producing cells were assessed by in vitro and in vivo experiments. IL-17+ infiltrates were not themselves predictive of an unfavourable clinical outcome, but correlated with infiltration by CD8+ T cells and CD16+ MPO+ neutrophils. Ex vivo analysis showed that tumour-infiltrating IL-17+ cells mostly consist of CD4+ T helper 17 (Th17) cells with multifaceted properties. Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release. Consistent with these findings, the presence of intraepithelial, but not of stromal Th17 cells, positively correlated with improved survival. Our study shows the dual role played by tumour-infiltrating Th17 in CRC, thus advising caution when developing new IL-17/Th17 targeted treatments.
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影响因子：
8.8
作者：
通讯作者：
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影响因子：
5.8
作者：
Middleton, Gary W.;Annels, Nicola E.;Pandha, Hardev S.
通讯作者：
Pandha, Hardev S.
影响因子：
4.4
作者：
Kryczek, Ilona;Wu, Ke;Zou, Weiping
通讯作者：
Zou, Weiping
影响因子：
64.8
作者：
Grivennikov, Sergei I.;Wang, Kepeng;Mucida, Daniel;Stewart, C. Andrew;Schnabl, Bernd;Jauch, Dominik;Taniguchi, Koji;Yu, Guann-Yi;Oesterreicher, Christoph H.;Hung, Kenneth E.;Datz, Christian;Feng, Ying;Fearon, Eric R.;Oukka, Mohamed;Tessarollo, Lino;Coppola, Vincenzo;Yarovinsky, Felix;Cheroutre, Hilde;Eckmann, Lars;Trinchieri, Giorgio;Karin, Michael
通讯作者：
Karin, Michael
影响因子：
20.3
作者：
Beriou, Gaelle;Costantino, Cristina M.;Hafler, David A.
通讯作者：
Hafler, David A.