title: Surgical trauma induces postoperative T-cell dysfunction in lung cancer patients through the programmed death-1 pathway.
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.
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai, 200032, People's Republic of China.
authors.forename: Pingbo
authors.initials: P
authors.lastname: Xu
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai, 200032, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai, 200032, People's Republic of China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai, 200032, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai, 200032, People's Republic of China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai, 200032, People's Republic of China. changhongmiaosh@163.com.
authors.forename: Changhong
authors.initials: C
authors.lastname: Miao
mesh_terms: D017209:Apoptosis; D060890:B7-H1 Antigen / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology* / Q000601:surgery*; D008213:Lymphocyte Activation; D011184:Postoperative Period; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Immunosuppression; Lung cancer; PD-1/PD-L1; Surgery