Intratumoral CD103+CD4+ T cell infiltration defines immunoevasive contexture and poor clinical outcomes in gastric cancer patients. (1st January 2020)

• Record Type: Journal Article
• Authors: Gu, Yun; Chen, Yifan; Jin, Kaifeng; Cao, Yifan; Liu, Xin; Lv, Kunpeng; He, Xudong; Lin, Chao; Liu, Hao; Li, He; He, Hongyong; Qin, Jing; Li, Ruochen; Zhang, Heng; Zhang, Weijuan
• Is Part Of: Oncoimmunology. Volume 9:Number 1(2020)
• Publication Date: 2020-01-01
• Subjects: Gastric cancer -- CD103+CD4+ T cell -- adjuvant therapy -- prognosis; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2020.1844402
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Our previous study has identified intratumoral CD103 + CD8 + T cells as a favorable prognostic factor in gastric cancer. However, the significance of CD103 + CD4 + T cells in gastric cancer hasn't yet been elucidated. Here, we aimed to investigate the clinical significance and phenotype characteristics of intratumoral CD103 + CD4 + T cells in gastric cancer. In our study, 469 formalin-fixed and paraffin-embedded samples and 24 fresh tissue specimens of patients with gastric cancer from Zhongshan Hospital were included. We manifested that intratumoral CD103 + CD4 + T cells in gastric cancer predicted poor overall survival and inferior responsiveness to fluorouracil-based ACT. The density and phenotypic characteristics of CD103 + CD4 + T cells in gastric cancer were detected by immunohistochemistry and flow cytometry, which showed that CD103 + CD4 + T cells exhibited an immunosuppressive phenotype and higher retention capacity in tumor tissues. Furthermore, increased CD103 + CD4 + T cells contributed to CD8 + T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Overall, this study revealed that intratumoral CD103 + CD4 + T cell infiltration defined immunoevasive contexture and predicted poor prognosis and inferior responsiveness to fluorouracil-based ACT. Therefore, we recommended that CD103 + CD4 + T cells might be a potential immunotherapeutic target for gastric cancer.