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

Abstract

Background

Tumor IL17-producing (IL17A⁺) cells infiltration has different prognostic value among various cancers. The objective of this study was to assess the effect of IL17A⁺ cells in gastric cancer.

Patients and methods

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).

Results

The infiltration of IL17A⁺ cells was positively correlated with the expression of IL17A mRNA (Spearman's r = 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 TNMII/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 anti-tumor 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 genes expression.

Conclusions

IL17A mRNA expression and intratumoral IL17A⁺ cells infiltration was correlated with anti-tumor 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.

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