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Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune
Suppression After Severe Sepsis/Septic Shock
#MMPMID27163951
Mathias B
; Delmas AL
; Ozrazgat-Baslanti T
; Vanzant EL
; Szpila BE
; Mohr AM
; Moore FA
; Brakenridge SC
; Brumback BA
; Moldawer LL
; Efron PA
Ann Surg
2017[Apr]; 265
(4
): 827-834
PMID27163951
show ga
OBJECTIVE: We hypothesized that after sepsis in humans, MDSCs will be
persistently increased, functionally immunosuppressive, and associated with
adverse clinical outcomes. BACKGROUND: Cancer 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.
METHODS: Blood 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.
RESULTS: After 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).
CONCLUSIONS: After 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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