Department of Gastric Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Ann Oncol. 2019 Feb 1;30(2):266-273. doi: 10.1093/annonc/mdy505.
Tumor IL17-producing (IL17A+) cells infiltration has different prognostic values among various cancers. The objective of this study was to assess the effect of IL17A+ cells in gastric cancer.
The study included two patient cohorts, the Cancer Genome Atlas cohort (TCGA, n = 351) and the Zhongshan Hospital cohort (ZSHC, n = 458). The TCGA and ZSHC were used for mRNA-related and cells infiltration-related analyses, respectively. The roles of IL17A mRNA and IL17A+ 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 IL17A+ cells infiltration (the preliminary Zhongshan Hospital cohort, PZSHC, n = 21).
The infiltration of IL17A+ cells was positively correlated with the expression of IL17A mRNA (Spearman's ρ = 0.811; P < 0.001). High IL17A mRNA expression and intratumoral IL17A+ 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 IL17A+ cells or lower peritumoral IL17A+ cells can benefit more from ACT. Elevated IL17A mRNA expression and increased intratumoral IL17A+ 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.
IL17A mRNA expression and intratumoral IL17A+ cells infiltration were correlated with antitumor immune contexture. IL17A+ 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.
肿瘤中产生白细胞介素 17A（IL17A）+细胞的浸润在不同癌症中有不同的预后价值。本研究的目的是评估 IL17A+细胞在胃癌中的作用。
本研究纳入了两个患者队列，癌症基因组图谱队列（TCGA，n=351）和中山医院队列（ZSHC，n=458）。TCGA 和 ZSHC 分别用于 mRNA 相关和细胞浸润相关分析。评估了 IL17A mRNA 和 IL17A+细胞在总生存期（OS）、辅助化疗反应（ACT）和免疫微环境中的作用。另一个独立队列用于确定 IL17A mRNA 和 IL17A+细胞浸润之间的相关性（初步中山医院队列，PZSHC，n=21）。
IL17A+细胞的浸润与 IL17A mRNA 的表达呈正相关（Spearman's ρ=0.811；P<0.001）。高 IL17A mRNA 表达和肿瘤内 IL17A+细胞与改善 OS 相关，并且在调整混杂因素后仍然具有统计学意义。TNM II/III 期疾病患者，其肿瘤内存在较高的肿瘤内 IL17A+细胞或较低的肿瘤旁 IL17A+细胞，可从 ACT 中获益更多。升高的 IL17A mRNA 表达和增加的肿瘤内 IL17A+细胞浸润与更多的抗肿瘤肥大细胞和自然杀伤细胞浸润以及更少的促肿瘤 M2 巨噬细胞浸润相关。高 IL17A mRNA 表达代表 Th17 细胞特征和免疫反应过程，与细胞毒性 GZMA、GZMB、IFNG、PRF1 和 TNFSF11 的表达增加相关。
IL17A mRNA 表达和肿瘤内 IL17A+细胞浸润与抗肿瘤免疫微环境相关。IL17A+细胞浸润可作为 OS 的独立预后生物标志物和 ACT 反应良好的预测生物标志物，需要进一步进行前瞻性验证。
