Intratumoral IL17-producing cells infiltration correlate with antitumor immune contexture and improved response to adjuvant chemotherapy in gastric cancer

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.