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



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.



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.



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.
Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
Jiali
J
Zhang
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, PR China.
Jing
J
Xu
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, PR China.
Rong-Xin
RX
Zhang
Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University , Guangzhou, PR China.
Yi
Y
Zhang
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, PR China.
Qing-Jian
QJ
Ou
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, PR China.
Jin-Qing
JQ
Li
Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University , Guangzhou, PR China.
Ze-Zhou
ZZ
Jiang
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, PR China.
Xiao-Jun
XJ
Wu
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center , Guangzhou, PR China.
Yu-Jing
YJ
Fang
Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
Limin
L
Zheng
CD169; T cell; cytolytic; phenotype; prognosis