CD169 identifies an activated CD8+ T cell subset in regional lymph nodes that predicts favorable prognosis in colorectal cancer patients

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.