CD169 identifies an activated CD8+ T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients. (2nd July 2016)

• Record Type: Journal Article
• Authors: Zhang, Jiali; Xu, Jing; Zhang, Rong-xin; Zhang, Yi; Ou, Qing-jian; Li, Jin-qing; Jiang, Ze-zhou; Wu, Xiao-jun; Fang, Yu-jing; Zheng, Limin
• Is Part Of: Oncoimmunology. Volume 5:Number 7(2016)
• Publication Date: 2016-07-02
• Subjects: CD169 -- cytolytic -- phenotype -- prognosis -- T cell; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2016.1177690
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Purpose: CD169 was first identified on macrophages (Mφ) and linked to antigen presentation. Here, we showed CD169 expression on some CD8 + T lymphocytes in regional lymph nodes (LNs) and investigated the function and clinical relevance of CD169 + CD8 + T cells in tumor-draining LNs of colorectal cancer (CRC) patients.Experimental design : Fresh tumor-draining LN tissues from 39 randomly enrolled patients were assessed by flow cytometry for activation and differentiation of CD169 + CD8 + T cells and T cell-mediated killing of tumor cells. In total, 114 tumor-draining LN paraffin sections from CRC patients were analyzed by multiple-color immunofluorescence for CD169 + CD8 + T cell distribution and clinical values. The prognostic significance of CD169 + CD8 + T cells was evaluated by Kaplan–Meier analysis.Results : A fraction of CD8 + T cells in regional LNs, but not peripheral blood, tonsils, or tumors, expressed surface CD169. In situ detection of draining LNs revealed preferential localization of CD169 + CD8 + T cells to subcapsular sinus and interfollicular regions, closely associated with CD169 + Mφ. CD169 + CD8 + T cell ratios were significantly lower in peri-tumor LNs than distant-tumor LNs. CD169 + CD8 + T cells predominantly expressed activation markers (CD69, HLA-DR, PD-1) with slightly lower CD45RA and CD62L levels. They produced high granzyme B, perforin, TNF-α, and IFNγ levels, and promoted tumor-killing efficiency ex vitro . Moreover, CD169 + CD8 + T cells infiltrating tumor-draining LNs decreased with disease progression and were strongly associated with CRC patient survival.Conclusions : We identified novel activated/cytolytic CD169 + CD8 + T cells selectively present in regional LNs, potentially serving as a powerful prognostic factor and indicator for selecting patients for immunotherapy.