title: 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.
authors.affiliation: 1] Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Cancer Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Cancer Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: J
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Cancer Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital and Cancer Institute, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1] Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054353:Perforin; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes
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