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Updated: Jun 12, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
ASSOCIATION BETWEEN LONGITUDINAL CHANGES IN SERUM SOLUBLE PD-L1 LEVELS AND NEUTROPHIL PD-L1 MRNA EXPRESSION WITH
Stelios Kokkoris1, Chrysi Keskinidou, Edison Jahaj
11 Department of Critical Care Medicine, Medical School, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece.
Abstract:
Introduction: Immunosuppression is a common phenomenon in critically ill patients, regardless of sepsis presence. The interaction between programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) is believed to play a significant role in immunosuppression. The primary aim of this study was to investigate the association between the dynamic changes of two negative co-stimulatory markers, neutrophil PD-L1 mRNA expression and serum soluble PD-L1 (sPD-L1) levels, and clinical outcome in a heterogeneous population of patients admitted to a general intensive care unit (ICU). Methods : This prospective study included critically ill patients admitted to a multidisciplinary ICU. Baseline levels of interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α were measured. Serum sPD-L1 and neutrophil PD-L1 mRNA relative expression were measured within 24-48 h of admission (baseline) and on days 4, 8, and 13, using ELISA. Data were analyzed using mixed-effects linear and logistic regression models. Results : A total of 42 patients were included in the final analysis, with 25 (60%) being male. The median age (IQR) was 57 (41-71) years, and the median APACHE II and SOFA scores were 16 (12-20) and 8 (7-10), respectively. Trauma was the admission diagnosis for 21 (50%) patients, and the all-cause ICU mortality rate was 35%. Admission serum sPD-L1 was positively correlated with C-reactive protein and IL-6, 8 and 10. Baseline neutrophil PD-L1 mRNA expression was positively correlated with γ-globulins and TNF-α. The longitudinal change in serum sPD-L1 levels was identified as an independent risk factor for ICU mortality (OR: 2.58, 95% CI: 1.17-5.72, P = 0.02). Conclusion : The dynamic change in serum sPD-L1 levels over time was independently associated with ICU outcome, highlighting their potential role as a prognostic marker. It could also guide immunomodulatory treatment in critically ill patients with severe immunosuppression.
