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PD-1(+) CD8(+) T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients.

ABSTRACT: BACKGROUND: The blockade of PD-1-PD-L1 pathway is emerging as an effective therapeutic strategy for several advanced cancers. But the immune regulatory role of PD-1-PD-L1 pathway is not clear in colorectal cancer (CRC) patients. This study aims to evaluate the role of PD-1-PD-L1 pathway in CD8(+) T-cell functions in tumour-draining lymph nodes (TDLNs) and tumours of CRC patients. METHODS: PD-1 expression on CD8(+) T cells was examined by flow cytometry, and PD-L1 expression in TDLNs and tumour tissues were examined by immunohistochemistry. Production of IFN-γ, IL-2 and expression of granzyme B, perforin in CD8(+) T cells were detected by intracellular staining. RESULTS: PD-1 expression is markedly upregulated on CD8(+) T cells in TDLNs and tumours compared with that in peripheral blood. PD-1-expressing CD8(+) T cells are competent for production of cytokine (IL-2 and IFN-γ) and perforin in the tumour-free lymph nodes (TFLNs), but exhibit exhausted phenotypes in tumours. In addition, PD-L1 is highly expressed in tumours rather than TFLNs, which is closely correlated with the impairment of IFN-γ production of tumour-infiltrating PD-1(+) CD8(+) T cells. CONCLUSIONS: Our findings suggest a suppressive effect of PD-1 on CD8(+) T-cell function in tumours, but not in TFLNs.

SUBMITTER: Wu X

PROVIDER: S-EPMC4183848 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other

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