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

Abstract

Background: Tumor IL17-producing (IL17A þ) cells infiltration has different prognostic values among various cancers. The objective of this study was to assess the effect of IL17A þ cells in gastric cancer. Patients and methods: The study included two patient cohorts, the Cancer Genome Atlas cohort (TCGA, n ¼ 351) and the Zhongshan Hospital cohort (ZSHC, n ¼ 458). The TCGA and ZSHC were used for mRNA-related and cells infiltration-related analyses, respectively. The roles of IL17A mRNA and IL17A þ 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 þ cells infiltration (the preliminary Zhongshan Hospital cohort, PZSHC, n ¼ 21). Results: The infiltration of IL17A þ cells was positively correlated with the expression of IL17A mRNA (Spearman's q ¼ 0.811; P < 0.001). High IL17A mRNA expression and intratumoral IL17A þ 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 þ cells or lower peritumoral IL17A þ cells can benefit more from ACT. Elevated IL17A mRNA expression and increased intratumoral IL17A þ 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 IL17A þ cells infiltration were correlated with antitumor immune contexture. IL17A þ 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.

Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer

“…However, in the present study, there were no significant correlations between IL‐17‐producing cells and DFS. Although the discrepancy might be as a result of the limited sample of NSCLC patients, it has been reported that higher intratumoral IL‐17A + cells were associated with better OS in patients with gastric cancer who received adjuvant chemotherapy, and γδT17 cells could enhance the efficacy of anticancer chemotherapy, indicating that IL‐17‐producing cells in NSCLC patients may contribute to cancer therapy, resulting in the prolonged OS. In our case, we found that patients who underwent surgery had better OS compared to patients who received chemotherapy (Figure A‐C).…”

Prediction of overall survival in resectable intrahepatic cholangiocarcinoma: ISICC‐applied prediction model

“…Tumor‐infiltrating lymphocytes have been shown to be a determinant of carcinogenesis and progression, and may also serve as a predictor of patient response to neoadjuvant chemotherapy . Wang et al reported that IL‐17A + immune cell infiltration was correlated with antitumor immune contexture and improved response to adjuvant chemotherapy in gastric cancer. In addition, Nywening et al revealed that dual targeting of tumor‐associated CCR2 + macrophages and CXCR2 + neutrophils could improve chemotherapeutic responses and enhance antitumor immunity by disrupting myeloid recruitment in pancreatic ductal adenocarcinoma.…”

<p>Outcomes of Adding Induction Chemotherapy to Concurrent Chemotherapy for Nasopharyngeal Carcinoma Patients with Moderate-Risk in the Intensity-Modulated Radiotherapy Era</p>

“…34 Infiltrating lymphocytes (IL)17Aþ cells infiltration could be used as an independent prognostic biomarker for OS and predictive biomarker for superior response to adjuvant chemotherapy. 35 Stromal immunotype predict survival and benefit from adjuvant chemotherapy in patients with muscle-invasive bladder cancer. 36 TIL, immunotype might predict the response to chemotherapy.…”