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.