Early Elevation of Monocytic-to-Polymorphonuclear Myeloid-Derived Suppressor Cells Ratio in Critical Illness is Associated with Favorable Clinical Outcomes.

Abstract

Background: Myeloid-derived suppressor cells (MDSCs), comprising polymorphonuclear (PMN-MDSCs) and monocytic subsets (M-MDSCs), are immunosuppressive immature myeloid cells implicated in disease progression and prognosis across multiple pathologies.

Purpose: To investigate the clinical significance of early MDSCs subset expansion in critical illness and identify novel prognostic biomarkers for risk stratification.

Patients and methods: This prospective study enrolled 85 critically ill adults (APACHE II ≥15), stratified into survivors (n=47) and non-survivors (n=38). MDSCs subsets were quantified via flow cytometry. Concurrent measurements included lactate, IL-6, CRP, lymphocyte subsets, and Tregs. Primary outcomes were 28-day all-cause mortality and secondary infection rates.

Results: Survivors exhibited significantly higher M-MDSCs% (median [IQR]: 4.824 [1.863-9.776] vs 2.503 [1.480-5.224], P<0.05) and elevated M-MDSCs/PMN-MDSCs ratios (122.166 [34.220-307.500] vs 28.324 [5.042-88.128], P<0.01). Patients with M-MDSCs/PMN-MDSCs ratios ≥85.765 demonstrated markedly lower mortality (23.08% vs 59.19%; hazard ratio [HR] = 3.530, 95% confidence interval [CI]: 1.668-7.467, P<0.001), with the low-ratio group exhibiting a 2.56-fold higher mortality risk. A combined stratification model (M-MDSCs/PMN-MDSCs + APACHE II score) revealed a 7.48-fold increase in mortality in the low-ratio/high-APACHE II subgroup compared to the high-ratio/low-APACHE II subgroup (86.36% vs 11.54%, P<0.001).

Conclusion: Elevated levels of M-MDSCs in the early stages of critical illness may exert protective effects. The ratio of M-MDSCs/PMN-MDSCs demonstrates predictive value for 28-day mortality, positioning it as a potential biomarker for prognostic assessment, but further multicenter studies are still needed to validate it.