Original article: PDF OnlyInduction of T helper 17 cell response by interleukin-7 in patients with primary cutaneous melanomaHe, Hongxiaa,,#; Qiao, Binjunb,,#; Guo, Shupinga; Cui, Hongzhoua; Li, Ningc; Liu, Hongyea; Qin, Junxiad; He, Jinghonge; Yang, Xiaofenga; Xue, Wenlia; Wang, YanzhenfAuthor Information aDepartment of Dermatology bDepartment of Emergency cDepartment of Pathology, The First Hospital of Shanxi Medical University dDepartment of Dermatology, The Affiliated Shanxi Provincial People’s Hospital of Shanxi Medical University eDepartment of Radiology, The First Hospital of Shanxi Medical University fDepartment of Rehabilitation, Children’s Hospital of Shanxi Province, Taiyuan, Shanxi Province, China # Hongxia He and Binjun Qiao contributed equally to the writing of this article. Received 4 March 2021 Accepted 16 April 2021 Correspondence to Hongxia He, MM, Department of Dermatology, The First Hospital of Shanxi Medical University, 85 South Jiefang Road, Taiyuan, 030000, Shanxi Province, China, Tel/fax: +86 351 4639549; e-mail: [email protected] Melanoma Research: May 28, 2021 - Volume Publish Ahead of Print - Issue - doi: 10.1097/CMR.0000000000000751 Buy PAP Metrics Abstract Interleukin (IL)-7 plays a vital role in proliferation and activation of T cells, however, its signaling through CD127 is impaired in T cells in cancers and chronic infections. The mechanisms underlying T helper 17 (Th17) cell responses by IL-7 in melanoma remain not fully understood. The aim of this study was to assess the effect of IL-7 signaling on Th17 responses in patients with primary cutaneous melanoma. Healthy and primary cutaneous melanoma donors were selected for this study of Th17 cell function. IL-17+CD4+ Th17 cells and CD127 expression on Th17 cells were determined by flow cytometry. Cytokine level was measured by ELISA. Peripheral and tissue-infiltrating CD4+ T cells were isolated using magnetic beads, and then stimulated with IL-7 and/or signal transducer and activator of transcription 5 inhibitor. Activated signaling molecules were analyzed by flow cytometry. Peripheral and tumor-infiltrating Th17 cells percentage was decreased, while peripheral IL-7 level was also reduced in melanoma patients. There was no significant difference of CD127 expression on Th17 cells between melanoma patients and controls. Antiapoptotic protein Bcl-2 was downregulated, whereas proapoptotic protein-activated caspase-3 was upregulated in peripheral and tissue-infiltrating Th17 cells in melanoma patients. Higher concentration of IL-7 (10 ng/mL), but not lower IL-7 concentration (1 ng/mL), promoted Bcl-2 expression and decreased caspase-3 expression in Th17 cells in melanoma patients. Inhibition of signal transducer and activator of transcription 5 resulted in the downregulation of Bcl-2 while upregulation of caspase-3 in Th17 cells. The present data suggested that reduced IL-7 responsiveness might be insufficient for Th17 activation in patients with primary cutaneous melanoma. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.