Intratumoral IL17-producing cells infiltration correlate with antitumor immune contexture and improved response to adjuvant chemotherapy in gastric cancer
Intratumoral IL17-producing cells infiltration correlate with antitumor immune contexture and improved response to adjuvant chemotherapy in gastric cancer
复制标题
瘤内产生 IL17 的细胞浸润与抗肿瘤免疫环境相关，并改善胃癌辅助化疗的反应
DOI：
10.1093/annonc/mdy505
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发表时间：
2019-02-01
影响因子：
50.5
通讯作者：
Xu, J. J.
中科院分区：
文献类型：
--
作者：
Wang, J. T.;Li, H.;Xu, J. J.
背景：肿瘤IL 17-产生细胞（IL 17 Athorn）浸润在不同癌症中具有不同的预后价值。本研究的目的是评估IL 17 Athorn细胞在胃癌中的作用。患者和方法：该研究包括两个患者队列，癌症基因组图谱队列（TCGA，n 1/4 351）和中山医院队列（ZSHC，n 1/4 458）。TCGA和ZSHC分别用于mRNA相关分析和细胞浸润相关分析。评价IL 17 A mRNA和IL 17 Athorn细胞在总生存期（OS）、辅助化疗（ACT）应答和免疫结构中的作用。另一个独立队列（中山医院初步队列，PZSHC，n 1/4 21）被纳入以鉴定IL 17 A mRNA与IL 17 Athorn细胞浸润之间的相关性。结果：IL 17 A Thorn细胞浸润与IL 17 A mRNA表达呈正相关（斯皮尔曼q1/4 0.811，P<0.0 0 1）。高IL 17 A mRNA表达和肿瘤内IL 17 A Thorn细胞与OS改善相关，在校正混杂因素后仍具有显著性。肿瘤内IL 17 Athorn细胞较高或瘤周IL 17 Athorn细胞较低的TNM II/III期患者可从ACT中获益更多。IL 17 A mRNA表达升高和肿瘤内IL 17 A Thorn细胞浸润增加与更多的抗肿瘤肥大细胞和自然杀伤细胞浸润以及较少的促肿瘤M2巨噬细胞浸润相关。高IL 17 A mRNA表达代表Th 17细胞特征和免疫应答过程，并且与细胞毒性GZMA、GZMB、IFNG、PRF 1和TNFSF 11表达增加相关。结论：IL 17 AmRNA表达及瘤内IL 17 Athorn细胞浸润与肿瘤免疫状态有关。IL 17-Athorn细胞浸润可作为一个独立的OS预后指标和ACT上级疗效的预测指标，有待进一步的前瞻性验证。
Background: Tumor IL17-producing (IL17Athorn) cells infiltration has different prognostic values among various cancers. The objective of this study was to assess the effect of IL17Athorn cells in gastric cancer. Patients and methods: The study included two patient cohorts, the Cancer Genome Atlas cohort (TCGA, n 1/4 351) and the Zhongshan Hospital cohort (ZSHC, n 1/4 458). The TCGA and ZSHC were used for mRNA-related and cells infiltration-related analyses, respectively. The roles of IL17A mRNA and IL17Athorn cells in overall survival (OS), response to adjuvant chemotherapy (ACT), and immune contexture were evaluated. Another independent cohort was included to identify the correlation between mRNA of IL17A and IL17Athorn cells infiltration (the preliminary Zhongshan Hospital cohort, PZSHC, n 1/4 21). Results: The infiltration of IL17Athorn cells was positively correlated with the expression of IL17A mRNA (Spearman's q 1/4 0.811; P< 0.001). High IL17A mRNA expression and intratumoral IL17Athorn cells were correlated with improved OS and remained to be significant after adjusted for confounders. Patients with TNM II/III disease whose tumor present higher intratumoral IL17Athorn cells or lower peritumoral IL17Athorn cells can benefit more from ACT. Elevated IL17A mRNA expression and increased intratumoral IL17Athorn cells infiltration was associated with more antitumor mast cells and nature killer cells infiltration and less pro-tumor M2 macrophages infiltration. High IL17A mRNA expression represented a Th17 cells signature and immune response process and was correlated with increased cytotoxic GZMA, GZMB, IFNG, PRF1, and TNFSF11 expression. Conclusions: IL17A mRNA expression and intratumoral IL17Athorn cells infiltration were correlated with antitumor immune contexture. IL17Athorn cells infiltration could be used as an independent prognostic biomarker for OS and predictive biomarker for superior response to ACT, and further prospective validation needs to be conducted.