Surgical trauma induces postoperative T-cell dysfunction in lung cancer patients through the programmed death-1 pathway
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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.
KeywordsPD-1/PD-L1 Surgery Immunosuppression Lung cancer
Peripheral blood monocyte cells
Programmed death ligand-1
Programmed death ligand-2
Tumor necrosis factor alpha
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.
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