Novel Identification of Myeloid-Derived Suppressor Cells in Children With Septic Shock.
Journal
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
ISSN: 1529-7535
Titre abrégé: Pediatr Crit Care Med
Pays: United States
ID NLM: 100954653
Informations de publication
Date de publication:
01 12 2022
01 12 2022
Historique:
pubmed:
13
9
2022
medline:
6
12
2022
entrez:
12
9
2022
Statut:
ppublish
Résumé
Immunoparalysis in children with septic shock is associated with increased risk of nosocomial infections and death. Myeloid-derived suppressor cells (MDSCs) potently suppress T cell function and may perpetuate immunoparalysis. Our goal was to test the hypothesis that children with septic shock would demonstrate increased proportions of MDSCs and impaired immune function compared with healthy controls. Prospective observational study. Fifty-four bed PICU in a quaternary-care children's hospital. Eighteen children with septic shock and thirty age-matched healthy children. None. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and stained for cell surface markers to identify MDSCs by flow cytometric analysis, including granulocytic and monocytic subsets. Adaptive and innate immune function was measured by ex vivo stimulation of whole blood with phytohemagglutinin-induced interferon (IFN) γ production and lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production, respectively. Prolonged organ dysfunction (OD) was defined as greater than 7 days. Children with septic shock had a higher percentage of circulating MDSCs, along with lower LPS-induced TNFα and phytohemagglutinin-induced IFNγ production capacities, compared with healthy controls. A cut-off of 25.2% MDSCs of total PBMCs in initial samples was optimal to discriminate children with septic shock who went on to have prolonged OD, area under the curve equal to 0.86. Children with prolonged OD also had decreased TNFα production capacity over time compared with those who recovered more quickly ( p = 0.02). This article is the first to describe increased MDSCs in children with septic shock, along with an association between early increase in MDSCs and adverse OD outcomes in this population. It remains unclear if MDSCs play a causative role in sepsis-induced immune suppression in children. Additional studies are warranted to establish MDSC as a potential therapeutic target.
Identifiants
pubmed: 36094492
doi: 10.1097/PCC.0000000000003071
pii: 00130478-202212000-00019
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
Phytohemagglutinins
0
Lipopolysaccharides
0
Types de publication
Observational Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e555-e563Informations de copyright
Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
Déclaration de conflit d'intérêts
Dr. Hall received funding from Abbvie, La Jolla Pharmaceuticals, and Kiadis. The remaining authors have disclosed that they do not have any potential conflicts of interest.
Références
Dellinger RP, Levy MM, Carlet JM, et al.; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine: Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296–327
Weiss SL, Fitzgerald JC, Pappachan J, et al.; Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network: Global epidemiology of pediatric severe sepsis: The sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med 2015; 191:1147–1157
Wong HR, Cvijanovich NZ, Anas N, et al.: Endotype transitions during the acute phase of pediatric septic shock reflect changing risk and treatment response. Crit Care Med 2018; 46:e242–e249
Hall MW, Knatz NL, Vetterly C, et al.: Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med 2011; 37:525–532
Muszynski JA, Nofziger R, Moore-Clingenpeel M, et al.: Early immune function and duration of organ dysfunction in critically ill children with sepsis. Am J Respir Crit Care Med 2018; 198:361–369
Groth C, Hu X, Weber R, et al.: Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. Br J Cancer 2019; 120:16–25
Rodriguez PC, Hernandez CP, Quiceno D, et al.: Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med 2005; 202:931–939
Corzo CA, Cotter MJ, Cheng P, et al.: Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J Immunol 2009; 182:5693–5701
Lechner MG, Liebertz DJ, Epstein AL: Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol 2010; 185:2273–2284
Ostrand-Rosenberg S, Sinha P: Myeloid-derived suppressor cells: Linking inflammation and cancer. J Immunol 2009; 182:4499–4506
Rodriguez PC, Ernstoff MS, Hernandez C, et al.: Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 2009; 69:1553–1560
Fallah J, Diaz-Montero CM, Rayman P, et al.: Myeloid-derived suppressor cells in nonmetastatic urothelial carcinoma of bladder is associated with pathologic complete response and overall survival. Clin Genitourin Cancer 2020; 18:500–508
Iclozan C, Antonia S, Chiappori A, et al.: Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage small cell lung cancer. Cancer Immunol Immunother 2013; 62:909–918
Mathias B, Delmas AL, Ozrazgat-Baslanti T, et al.; the Sepsis, Critical Illness Research Center Investigators: Human myeloid-derived suppressor cells are associated with chronic immune suppression after severe sepsis/septic shock. Ann Surg 2017; 265:827–834
Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis: International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6:2–8
Bronte V, Brandau S, Chen SH, et al.: Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 2016; 7:12150
Apodaca MC, Wright AE, Riggins AM, et al.: Characterization of a whole blood assay for quantifying myeloid-derived suppressor cells. J Immunother Cancer 2019; 7:230
Pollack MM, Patel KM, Ruttimann UE: PRISM III: An updated rediatric risk of mortality score. Crit Care Med 1996; 24:743–752
Leteurtre S, Duhamel A, Salleron J, et al.; Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP): PELOD-2: An update of the PEdiatric logistic organ dysfunction score. Crit Care Med 2013; 41:1761–1773
McIntosh AM, Tong S, Deakyne SJ, et al.: Validation of the vasoactive-inotropic score in pediatric sepsis. Pediatr Crit Care Med 2017; 18:750–757
Hall MW, Geyer SM, Guo CY, et al.; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network PICFlu Study Investigators: Innate immune function and mortality in critically ill children with influenza: A multicenter study. Crit Care Med 2013; 41:224–236
Leukes VN, Dorhoi A, Malherbe ST, et al.: Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis. Cell Immunol 2021; 364:104359
Chen J, Ye Y, Liu P, et al.: Suppression of T cells by myeloid-derived suppressor cells in cancer. Hum Immunol 2017; 78:113–119
Qu P, Wang LZ, Lin PC: Expansion and functions of myeloid-derived suppressor cells in the tumor microenvironment. Cancer Lett 2016; 380:253–256
Sacchi A, Grassi G, Bordoni V, et al.: Early expansion of myeloid-derived suppressor cells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19 outcome. Cell Death Dis 2020; 11:921
Xue G, Jiang M, Zhao R, et al.: Elevated frequencies of CD14+HLA-DRlo/neg MDSCs in COVID-19 patients. Aging (Albany NY) 2021; 13:6236–6246
Reizine F, Lesouhaitier M, Gregoire M, et al.: SARS-CoV-2-induced ARDS associates with MDSC expansion, lymphocyte dysfunction, and arginine shortage. J Clin Immunol 2021; 41:515–525
Agrati C, Sacchi A, Bordoni V, et al.: Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19). Cell Death Differ 2020; 27:3196–3207
Draghiciu O, Lubbers J, Nijman HW, et al.: Myeloid derived suppressor cells-An overview of combat strategies to increase immunotherapy efficacy. Oncoimmunology 2015; 4:e954829