• Brittany Mathias, Amber L Delmas, Tezcan Ozrazgat-Baslanti, Erin L Vanzant, Benjamin E Szpila, Alicia M Mohr, Frederick A Moore, Scott C Brakenridge, Babette A Brumback, Lyle L Moldawer, Philip A Efron, and the Sepsis, Critical Illness Research Center Investigators.
• *Department of Surgery, University of Florida College of Medicine, Gainesville, FL †Department of Anesthesia, University of Florida College of Medicine, Gainesville, FL ‡Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL §The Sepsis and Critical Illness Research Center, University of Florida College of Medicine, Gainesville, FL.
• Ann. Surg. 2017 Apr 1; 265 (4): 827-834.

ObjectiveWe hypothesized that after sepsis in humans, MDSCs will be persistently increased, functionally immunosuppressive, and associated with adverse clinical outcomes.BackgroundCancer and sepsis have surprisingly similar immunologic responses and equally dismal long term consequences. In cancer, increased myeloid-derived suppressor cells (MDSCs) induce detrimental immunosuppression, but little is known about the role of MDSCs after sepsis.MethodsBlood was obtained from 74 patients within 12 hours of severe sepsis/septic shock (SS/SS), and at set intervals out to 28 days, and also in 18 healthy controls. MDSCs were phenotyped for cell surface receptor expression and enriched by cell sorting. Functional and genome-wide expression analyses were performed. Multiple logistic regression analysis was conducted to determine if increased MDSC appearance was associated with in-hospital and long-term outcomes.ResultsAfter SS/SS, CD33CD11bHLA-DR MDSCs were dramatically increased out to 28 days (P < 0.05). When co-cultured with MDSCs from SS/SS patients, antigen-driven T-cell proliferation and TH1/TH2 cytokine production were suppressed (P < 0.05). Additionally, septic MDSCs had suppressed HLA gene expression and up-regulated ARG1 expression (P < 0.05). Finally, SS/SS patients with persistent increased percentages of blood MDSCs had increased nosocomial infections, prolonged intensive care unit stays, and poor functional status at discharge (P < 0.05).ConclusionsAfter SS/SS in humans, circulating MDSCs are persistently increased, functionally immunosuppressive, and associated with adverse outcomes. This novel observation warrants further studies. As observed in cancer immunotherapy, MDSCs could be a novel component in multimodality immunotherapy targeting detrimental inflammation and immunosuppression after SS/SS to improve currently observed dismal long-term outcomes.

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