Surgical trauma induces postoperative T-cell dysfunction in lung cancer patients through the programmed death-1 pathway

Cancer Immunol Immunother. 2015 Nov;64(11):1383-92. doi: 10.1007/s00262-015-1740-2. Epub 2015 Jul 17.

Abstract

The programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) pathway have been shown to be involved in tumor-induced and sepsis-induced immunosuppression. However, whether this pathway is involved in the surgery-induced dysfunction of T lymphocytes is not known. Here, we analyzed expression of PD-1 and PD-L1 on human peripheral mononuclear cells during the perioperative period. We found that surgery increased PD-1/PD-L1 expression on immune cells, which was correlated with the severity of surgical trauma. The count of T lymphocytes and natural killer cells reduced after surgery, probably due to the increased activity of caspase-3. Caspase-3 level was positively correlated with PD-1 expression. Profile of perioperative cytokines and hormones in plasma showed a significantly increased level of interferon-α, as well as various inflammatory cytokines and stress hormones. In ex vivo experiments, administration of anti-PD-1 antibody significantly ameliorated T-cell proliferation and partially reversed the T-cell apoptosis induced by surgical trauma. We provide evidences that surgical trauma can induce immunosuppression through the PD-1/PD-L1 pathway. This pathway could be a target for preventing postoperative cellular immunosuppression.

Keywords: Immunosuppression; Lung cancer; PD-1/PD-L1; Surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • B7-H1 Antigen / physiology
  • Caspase 3 / metabolism
  • Cytokines / blood
  • Humans
  • Killer Cells, Natural / immunology
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / surgery*
  • Lymphocyte Activation
  • Postoperative Period
  • Programmed Cell Death 1 Receptor / analysis
  • Programmed Cell Death 1 Receptor / physiology*
  • Signal Transduction / physiology*
  • T-Lymphocytes / immunology*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Cytokines
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • CASP3 protein, human
  • Caspase 3