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Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Br+J+Cancer 2014 ; 111 (7): 1391-9 Nephropedia Template TP
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PD-1+ CD8+ T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients #MMPMID25093496
Wu X; Zhang H; Xing Q; Cui J; Li J; Li Y; Tan Y; Wang S
Br J Cancer 2014[Sep]; 111 (7): 1391-9 PMID25093496show ga
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-?, 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-?) 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-? 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.