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中华重症医学电子杂志 ›› 2025, Vol. 11 ›› Issue (02) : 198 -203. doi: 10.3877/cma.j.issn.2096-1537.2025.02.018

综述

PD-1/PD-L1 通路在脓毒症导致的脏器功能障碍中的作用
张优佳1, 丁明月1, 刘之琪1, 郑帅歌1, 刘仕豪1, 秦秉玉1,()   
  1. 1. 450003 郑州,郑州大学人民医院 河南省人民医院重症医学部
  • 收稿日期:2024-11-07 出版日期:2025-05-28
  • 通信作者: 秦秉玉

The role of the PD-1/PD-L1 pathway in organ dysfunction caused by sepsis

Youjia Zhang1, Mingyue Ding1, Zhiqi Liu1, Shuaige Zheng1, Shihao Liu1, Bingyu Qin1,()   

  1. 1. Department of Critical Care Medicine,Henan Provincial People's Hospital,People's Hospital of Zhengzhou University,Zhengzhou 450003,China
  • Received:2024-11-07 Published:2025-05-28
  • Corresponding author: Bingyu Qin
引用本文:

张优佳, 丁明月, 刘之琪, 郑帅歌, 刘仕豪, 秦秉玉. PD-1/PD-L1 通路在脓毒症导致的脏器功能障碍中的作用[J/OL]. 中华重症医学电子杂志, 2025, 11(02): 198-203.

Youjia Zhang, Mingyue Ding, Zhiqi Liu, Shuaige Zheng, Shihao Liu, Bingyu Qin. The role of the PD-1/PD-L1 pathway in organ dysfunction caused by sepsis[J/OL]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2025, 11(02): 198-203.

脓毒症是炎症、免疫激活、免疫抑制、缺氧等多种因素相互作用的结果,脓毒症可导致多器官功能障碍,具有较高的病死率。脓毒症在临床上的发生发展常受多重因素影响,程序性死亡受体配体1(PD-L1)已被证实可作为预测脓毒症病死率的一种新的预后生物标志物,然而其在脓毒症诱导的脏器功能障碍中的作用还未有定论。本文就程序性死亡受体1(PD-1)/PD-L1 通路在脓毒症病程进展中导致脏器功能障碍的最新研究作一综述,探讨阻断PD-1/PD-L1 通路在改善脓毒症患者脏器功能障碍中的前景。

Sepsis is the result of the interaction of multiple factors such as inflammation,immune activation,immune suppression,and hypoxia.Sepsis can lead to multiple organ dysfunction and has a high mortality rate.The clinical development of sepsis is often affected by multiple factors.PD-L1 has been proven to be a new prognostic biomarker for predicting mortality in sepsis.However,its role in sepsis-induced organ function The role of the PD-1/PD-L1 pathway in sepsis has not yet been determined.This review mainly introduces the latest research progress on the role of the PD-1/PD-L1 pathway in causing organ dysfunction in the progression of sepsis.To investigate whether blocking PD-1/PD-L1 pathway can improve organ dysfunction in patients with sepsis.

1
Singer M,Deutschman CS,Seymour CW,et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [J].JAMA,2016,315(8):801-810.
2
Fleischmann-Struzek C,Mellhammar L,Rose N,et al.Incidence and mortality of hospital- and ICU-treated sepsis:results from an updated and expanded systematic review and meta-analysis [J].Intensive Care Med,2020,46(8):1552-1562.
3
Almalki WH.The sepsis induced defective aggravation of immune cells:a translational science underling chemico-biological interactions from altered bioenergetics and/or cellular metabolism to organ dysfunction [J].Mol Cell Biochem,2021,476(6):2337-2344.
4
Jiang W,Li X,Wen M,et al.Increased percentage of PD-L1(+) natural killer cells predicts poor prognosis in sepsis patients:a prospective observational cohort study [J].Crit Care,2020,24(1):617.
5
Schöniger S,Jasani B.The PD-1/PD-L1 pathway:a perspective on comparative immuno-oncology [J].Animals (Basel),2022,12(19):2661.
6
Kythreotou A,Siddique A,Mauri FA,et al.PD-L1 [J].J Clin Pathol,2018,71(3):189-194.
7
Wherry EJ,Kurachi M.Molecular and cellular insights into T cell exhaustion [J].Nat Rev Immunol,2015,15(8):486-499.
8
Gao Y,Yang J,Cai Y,et al.IFN-γ-mediated inhibition of lung cancer correlates with PD-L1 expression and is regulated by PI3K-AKT signaling [J].Int J Cancer,2018,143(4):931-943.
9
Boomer JS,To K,Chang KC,et al.Immunosuppression in patients who die of sepsis and multiple organ failure [J].JAMA,2011,306(23):2594-2605.
10
Roquilly A,McWilliam HEG,Jacqueline C,et al.Local modulation of antigen-presenting cell development after resolution of pneumonia induces long-term susceptibility to secondary infections [J].Immunity,2017,47(1):135-147.e135.
11
Beltrán-García J,Osca-Verdegal R,Jávega B,et al.Characterization of early peripheral immune responses in patients with sepsis and septic shock [J].Biomedicines,2022,10(3):525.
12
Xu R,Liu X,Li A,et al.c-Met up-regulates the expression of PDL1 through MAPK/NF-κBp65 pathway [J].J Mol Med (Berl),2022,100(4):585-598.
13
Fernandes RA,Su L,Nishiga Y,et al.Immune receptor inhibition through enforced phosphatase recruitment [J].Nature,2020,586(7831):779-784.
14
Chemnitz JM,Parry RV,Nichols KE,et al.SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation,but only receptor ligation prevents T cell activation [J].J Immunol,2004,173(2):945-954.
15
Marasco M,Berteotti A,Weyershaeuser J,et al.Molecular mechanism of SHP2 activation by PD-1 stimulation [J].Sci Adv,2020,6(5):eaay4458.
16
Patsoukis N,Li L,Sari D,et al.PD-1 increases PTEN phosphatase activity while decreasing PTEN protein stability by inhibiting casein kinase 2 [J].Mol Cell Biol,2013,33(16):3091-3098.
17
Wang JF,Wang YP,Xie J,et al.Upregulated PD-L1 delays human neutrophil apoptosis and promotes lung injury in an experimental mouse model of sepsis [J].Blood,2021,138(9):806-810.
18
Liu J,Song K,Lin B,et al.HMGB1 promotes neutrophil PD-L1 expression through TLR2 and mediates T cell apoptosis leading to immunosuppression in sepsis [J].Int Immunopharmacol,2024,133:112130.
19
Hussain SM,Kansal RG,Alvarez MA,et al.Role of TGF-β in pancreatic ductal adenocarcinoma progression and PD-L1 expression[J].Cell Oncol (Dordr),2021,44(3):673-687.
20
Josefowicz SZ,Lu LF,Rudensky AY.Regulatory T cells:mechanisms of differentiation and function [J].Annu Rev Immunol,2012,30:531-564.
21
Grover P,Goel PN,Greene MI.Regulatory T cells:regulation of identity and function [J].Front Immunol,2021,12:750542.
22
Che YM,Zhang Y,Li M,et al.In vitro and in vivo effect of PD-1/PDL1 blockade on microglia/macrophage activation and T cell subset balance in cryptococcal meningitis [J].J Cell Biochem,2018,119(4):3044-3057.
23
Shao R,Fang Y,Yu H,et al.Monocyte programmed death ligand-1 expression after 3-4 days of sepsis is associated with risk stratification and mortality in septic patients:a prospective cohort study [J].Crit Care,2016,20(1):124.
24
Xia Q,Wei L,Zhang Y,et al.Immune checkpoint receptors Tim-3 and PD-1 regulate monocyte and T lymphocyte function in septic patients[J].Mediators Inflamm,2018,2018:1632902.
25
Hokama LT,Veiga ADM,Menezes MCS,et al.Endothelial injury in COVID-19 and septic patients [J].Microvasc Res,2022,140:104303.
26
Cahill PA,Redmond EM.Vascular endothelium - Gatekeeper of vessel health [J].Atherosclerosis,2016,248:97-109.
27
Yang X,Chang Y,Wei W.Endothelial dysfunction and inflammation:immunity in rheumatoid arthritis [J].Mediators Inflamm,2016,2016:6813016.
28
Smeding L,Plötz FB,Groeneveld AB,et al.Structural changes of the heart during severe sepsis or septic shock [J].Shock,2012,37(5):449-456.
29
Opal SM,van der Poll T.Endothelial barrier dysfunction in septic shock [J].J Intern Med,2015,277(3):277-293.
30
Hutchins NA,Wang F,Wang Y,et al.Kupffer cells potentiate liver sinusoidal endothelial cell injury in sepsis by ligating programmed cell death ligand-1 [J].J Leukoc Biol,2013,94(5):963-970.
31
Zhao S,Gao J,Li J,et al.Correction to:PD-L1 regulates inflammation in LPS-induced lung epithelial cells and vascular endothelial cells by interacting with the HIF-1α signaling pathway [J].Inflammation,2022,45(2):931-932.
32
Lomas-Neira J,Monaghan SF,Huang X,et al.Novel role for PD-1:PD-L1 as mediator of pulmonary vascular endothelial cell functions in pathogenesis of indirect ARDS in mice [J].Front Immunol,2018,9:3030.
33
Wang Z,Guo Z,Wang X,et al.Inhibition of EZH2 ameliorates sepsis acute lung injury (SALI) and non-small-cell lung cancer (NSCLC)proliferation through the PD-L1 pathway [J].Cells,2022,11(24):3958.
34
Curran CS,Busch LM,Li Y,et al.Anti-PD-L1 therapy does not improve survival in a murine model of lethal Staphylococcus aureus pneumonia [J].J Infect Dis,2021,224(12):2073-2084.
35
Liu S,Xie J,Duan C,et al.ADAR1 inhibits macrophage apoptosis and alleviates sepsis-induced liver injury through miR-122/BCL2A1 signaling [J].J Clin Transl Hepatol,2024,12(2):134-150.
36
Li M,Song K,Huang X,et al.GDF-15 prevents LPS and D-galactosamine-induced inflammation and acute liver injury in mice[J].Int J Mol Med,2018,42(3):1756-1764.
37
Liang X,Li T,Zhou Q,et al.Mesenchymal stem cells attenuate sepsisinduced liver injury via inhibiting M1 polarization of Kupffer cells [J].Mol Cell Biochem,2019,452(1-2):187-197.
38
Wang F,Huang X,Chung CS,et al.Contribution of programmed cell death receptor (PD)-1 to Kupffer cell dysfunction in murine polymicrobial sepsis [J].Am J Physiol Gastrointest Liver Physiol,2016,311(2):G237-245.
39
Triantafyllou E,Gudd CL,Mawhin MA,et al.PD-1 blockade improves Kupffer cell bacterial clearance in acute liver injury [J].J Clin Invest,2021,131(4).
40
Lu Y,Wang G,Li C.Expression of peripheral monocytic programmed death ligand-1 in severe sepsis combined with HBV-related cirrhosis.A pilot observational study [J].Cent Eur J Immunol,2021,46(2):217-224.
41
Gómez H,Kellum JA.Sepsis-induced acute kidney injury [J].Curr Opin Crit Care,2016,22(6):546-553.
42
Kawamoto E,Masui-Ito A,Eguchi A,et al.Integrin and PD-1 ligand expression on circulating extracellular vesicles in systemic inflammatory response syndrome and sepsis [J].Shock,2019,52(1):13-22.
43
Hu YM,Hsiung YC,Pai MH,et al.Glutamine administration in early or late septic phase downregulates lymphocyte PD-1/PD-L1 expression and the inflammatory response in mice with polymicrobial sepsis [J].JPEN J Parenter Enteral Nutr,2018,42(3):538-549.
44
Xu J,Ma X,Yu K,et al.Lactate up-regulates the expression of PD-L1 in kidney and causes immunosuppression in septic Acute Renal Injury[J].J Microbiol Immunol Infect,2021,54(3):404-410.
45
Patera AC,Drewry AM,Chang K,et al.Frontline science:defects in immune function in patients with sepsis are associated with PD-1 or PD-L1 expression and can be restored by antibodies targeting PD-1 or PD-L1 [J].J Leukoc Biol,2016,100(6):1239-1254.
46
Hotchkiss RS,Colston E,Yende S,et al.Immune checkpoint inhibition in sepsis:a phase 1b randomized,placebo-controlled,single ascending dose study of antiprogrammed cell death-ligand 1 antibody (BMS-936559) [J].Crit Care Med,2019,47(5):632-642.
47
Hotchkiss RS,Colston E,Yende S,et al.Immune checkpoint inhibition in sepsis:a Phase 1b randomized study to evaluate the safety,tolerability,pharmacokinetics,and pharmacodynamics of nivolumab[J].Intensive Care Med,2019,45(10):1360-1371.
48
Watanabe E,Nishida O,Kakihana Y,et al.Pharmacokinetics,pharmacodynamics,and safety of Nivolumab in patients with sepsisinduced immunosuppression:a multicenter,open-label phase 1/2 study[J].Shock,2020,53(6):686-694.
49
Valentine C,Bergerat A.Immunoprofiling determines survival and guides therapy in sepsis [J].J Immunol,2016,196(Suppl 1):194-196.
50
Chan KK,Bass AR.Autoimmune complications of immunotherapy:pathophysiology and management [J].BMJ,2020,369:m736.
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