Article ; Online: PD-1(+) CD8(+) T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients.
2014 Volume 111, Issue 7, Page(s) 1391–1399
Abstract: ... in tumour-draining lymph nodes (TDLNs) and tumours of CRC patients.: Methods: PD-1 expression on CD8 ... tumours compared with that in peripheral blood. PD-1-expressing CD8(+) T cells are competent ... by intracellular staining.: Results: PD-1 expression is markedly upregulated on CD8(+) T cells in TDLNs and ...
| 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. |
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| MeSH term(s) | Adult ; Aged ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Female ; Granzymes/metabolism ; Humans ; Interferon-gamma/metabolism ; Lymph Nodes/immunology ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Perforin/metabolism ; Programmed Cell Death 1 Receptor/metabolism ; Up-Regulation | |||||
| Chemical Substances | PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Perforin (126465-35-8) ; Interferon-gamma (82115-62-6) ; GZMB protein, human (EC 3.4.21.-) ; Granzymes (EC 3.4.21.-) | |||||
| Language | English | |||||
| Publishing date | 2014-08-05 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 80075-2 | |||||
| ISSN | 1532-1827 ; 0007-0920 | |||||
| ISSN (online) | 1532-1827 | |||||
| ISSN | 0007-0920 | |||||
| DOI | 10.1038/bjc.2014.416 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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