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

Br J Cancer. 2014 Sep 23;111(7):1391-9. doi: 10.1038/bjc.2014.416. Epub 2014 Aug 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Perforin
  • Interferon-gamma
  • GZMB protein, human
  • Granzymes