Cancer Immunology, Immunotherapy

, Volume 64, Issue 11, pp 1383–1392 | Cite as

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

  • Pingbo Xu
  • Ping Zhang
  • Zhirong Sun
  • Yun Wang
  • Jiawei Chen
  • Changhong Miao
Original Article

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

PD-1/PD-L1 Surgery Immunosuppression Lung cancer 

Abbreviations

DCs

Dendritic cells

IFN-α

Interferon alpha

IL

Interleukin

NK

Natural killer

PBMCs

Peripheral blood monocyte cells

PD-1

Programmed death-1

PD-L1

Programmed death ligand-1

PD-L2

Programmed death ligand-2

PGE2

Prostaglandin E2

POD

Postoperative day

TNF-α

Tumor necrosis factor alpha

Notes

Acknowledgments

Funding was received from National Natural Science Foundation of China (NSFC 81471852) and Shanghai Natural Science Foundation (KW 1307, KW142R1407500).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

262_2015_1740_MOESM1_ESM.pdf (135 kb)
Supplementary material 1 (PDF 135 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Pingbo Xu
    • 1
  • Ping Zhang
    • 2
  • Zhirong Sun
    • 1
  • Yun Wang
    • 1
  • Jiawei Chen
    • 1
  • Changhong Miao
    • 1
  1. 1.Department of AnesthesiologyFudan University Shanghai Cancer CenterShanghaiPeople’s Republic of China
  2. 2.Cancer InstituteFudan University Shanghai Cancer CenterShanghaiPeople’s Republic of China

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