| ObjectiveTo clarify the relationship between the expression of PD-1,TIGIT,and CD226 on T-cell and prognosis in patients with sepsis;to screen for prognostically relevant subgroups combining multiple T-cell immune checkpoints,compare clinical characteristics among subgroups,and identify the subgroup with the best predictive power to provide a scientific basis for stratifying the immune status and implementing targeted immunotherapy for sepsis patients.MethodsA multi-center,prospective,cohort study in intensive care unit of several general hospitals in Guangzhou had earlier enrolled patients according to the sepsis-3.0 criteria from November 2020 to November 2022.In the first 24 hours following enrollment,basic clinical data,critical illness-related scores,relevant biochemical indicators and nosocomial infection assessments during hospitalization were recorded from patients.Peripheral blood samples were collected within 24 hours post-recruitment,and flow cytometry was used to detect the expression of PD-1,TIGIT,and CD226 on T cells.Finally,patients were followed up for 28 days,and clinical characteristics of each subgroup were analyzed.Survival analysis was then used to evaluate the relationship between each immune subgroup and prognosis.ResultsA total of 261 patients were recruited,and 158 patients were finally included for final analysis.According to the 28-day mortality,patients were divided into survivors and non-survivors groups.The expression of PD-1 on CD4+T cells and CD8+T cells was significantly higher in the non-survivors than the survivors,while the expression of CD226 on CD8+T cells have the opposite tendency.The trachea cannula,SOFA scores,the percentage of PD-1 and CD226 on CD8+T cells were independent risk factors for 28-day mortality.The AUC of the percentage of PD-1 and CD226 on CD8+T cells,SOFA scores,PD-1/CD226 on CD8+T cells and Model were 0.639(0.540-0.738),0.619(0.531-0.707),0.691(0.594-0.787),0.671(0.578-0.765)and 0.772(0.686-0.858),respectively.The combination model was the indicator with the best AUC to predict mortality in 28 days(all p<0.05).Patients with the percentage of PD-1 on CD8+T cells above the cutoff point 0.164,CD226 below 0.684,SOFA above 11.5,PD-1/CD226 on CD8+T cells above 0.430,and Model above 0.318 were the indexes that had greater discriminative capacity to predict 28 days mortality and the patients’ risk of death was increased.Based on the high or low expression levels of PD-1 and CD226 in T cells,patients were divided into four groups:PD-lhiCD226low,PD-1hiCD226hi,PD-1lowCD226low,and PD-1low-CD226hi,respectively.Analysis revealed that the PD-lhiCD226low subgroup of T cells had the highest risk of death,and this result was not altered after adjusting for risk factors.The CD8+T PD-1lowCD226hi subgroup had the lowest risk of death,but there was no advantage for the CD4+T PD-1lowCD226hi subgroup in terms of prognosis.When CD226 was included as a parameter,subgroups of PD-1hi or PD-1low can be further stratified,indicating that the predictive value of multi-immune checkpoint combination for the prognosis of sepsis patients is superior to a single indicatorConclusionUp-regulation of PD-1 and down-regulation of CD226 on T cells in septic patients can predict poor prognosis,but there is no obvious relationship between TIGIT and prognosis.The combination of PD-1 and CD226 on CD8+T cells at day 1 identifies immune stratification and poor outcome in septic patients,and it is superior to a single marker for predicting prognosis. |
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