Tumor-infiltrating IL-17A+ cells determine favorable prognosis and adjuvant chemotherapeutic response in muscle-invasive bladder cancer

Zewei Wang; Quan Zhou; Han Zeng; Hongyu Zhang; Zhaopei Liu; Qiuren Huang; Ying Xiong; Jiajun Wang; Yuan Chang; Qi Bai; Yu Xia; Yiwei Wang; Yu Zhu; Le Xu; Bo Dai; Li Liu; Jianming Guo; Jiejie Xu

doi:10.1080/2162402X.2020.1747332

Tumor-infiltrating IL-17A⁺ cells determine favorable prognosis and adjuvant chemotherapeutic response in muscle-invasive bladder cancer

Oncoimmunology. 2020 Apr 10;9(1):1747332. doi: 10.1080/2162402X.2020.1747332. eCollection 2020.

Authors

Zewei Wang¹, Quan Zhou², Han Zeng², Hongyu Zhang², Zhaopei Liu², Qiuren Huang², Ying Xiong¹, Jiajun Wang¹, Yuan Chang³, Qi Bai¹, Yu Xia¹, Yiwei Wang⁴, Yu Zhu³, Le Xu⁵, Bo Dai³, Li Liu¹, Jianming Guo¹, Jiejie Xu²

Affiliations

¹ Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
³ Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁴ Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

The role of IL-17A⁺ cells remains controversial among various cancer types. This study aimed to investigate the effects of IL-17A⁺ cells on tumor immune contexture and clinical outcome in muscle-invasive bladder cancer (MIBC). In this study, we enrolled 141 patients from Zhongshan Hospital, 118 patients from Shanghai Cancer Center and 403 patients from TCGA cohort. In vitro studies were conducted in 32 freshly resected tumors. Survival analysis was conducted using Kaplan-Meier and Cox regression analysis. The results suggested that patients with high levels of IL-17A⁺ cells had prolonged overall survival and recurrence-free survival (HR = 0.268, P < .001; and HR = 0.433, P < .001). Moreover, these patients tended to be at lower risk of death and recurrence after adjuvant chemotherapy (P = .012 and P = .004). An increased number of IL-17A⁺ cells correlated with the infiltration of several anti-tumor immune cells into tumors. In addition, IL-17A⁺ cells had an influence on the recruitment, proliferation, and activation of CD8⁺ cells, and were positively associated with the expression of several anti-tumor effector cytokines. In conclusion, tumor-infiltrating IL17A⁺ cells were correlated with an elevated anti-tumor immunity in MIBC. Besides, high infiltration of IL17A⁺ cells can predict benefit from ACT for MIBC patients.

Keywords: IL-17A+ cells; adjuvant chemotherapy; anti-tumor immunity; muscle-invasive bladder cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemotherapy, Adjuvant
China / epidemiology
Humans
Interleukin-17 / therapeutic use
Muscles
Neoplasm Recurrence, Local / drug therapy
Prognosis
Urinary Bladder Neoplasms* / drug therapy

Substances

Interleukin-17

Grants and funding

This study was funded by grants from National Natural Science Foundation of China (31770851, 81702496, 81702497, 81702805, 81772696, 81872082, 81902556, 81902563, 81902898, 81974393), National Key R&D Program of China (2017YFC0114303), Shanghai Municipal Natural Science Foundation (16ZR1406500, 17ZR1405100, 19ZR1431800), Guide Project of Science and Technology Commission of Shanghai Municipality (17411963100), Shanghai Sailing Program (18YF1404500, 19YF1407900, 19YF1427200), Shanghai Municipal Commission of Health and Family Planning Program (20174Y0042, 201840168, 20184Y0151), Fudan University Shanghai Cancer Center for Outstanding Youth Scholars Foundation (YJYQ201802) and Shanghai Cancer Research Charity Center. All these study sponsors have no roles in the study design, in the collection, analysis, and interpretation of data.