Intratumoral IL17-producing cells infiltration correlate with anti-tumor immune contexture and improved response to adjuvant chemotherapy in gastric cancer
Menée à partir de données portant sur 2 cohortes incluant au total 809 patients atteints d'un cancer gastrique, cette étude met en évidence une corrélation entre l'infiltration de la tumeur par des cellules immunitaires sécrétrices d'interleukine IL-17, la présence plus ou moins grande d'autres cellules immunitaires dans la tumeur (mastocytes, cellules NK, macrophages M2, ...) et la réponse à une chimiothérapie adjuvante
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.
Annals of Oncology , résumé, 2017