Immunotherapy to treat sepsis induced-immunosuppression: Immune eligibility or outcome criteria, a systematic review.

Sepsis-induced immunosuppression (SIS) is the target of multiple clinical studies testing immunotherapies. To date, most trials are performed on a heterogeneous and unselected population. Without any consensual definition of immunosuppression and therapeutic goals, results from these trials remain poorly transposable. In this perspective, we conducted a systematic review aiming at 1/registering the inclusion criteria, 2/ report the outcomes evaluated in this literature. We searched Pubmed, Embase, and ClinicalTrials.gov for studies using an immunotherapy to reverse SIS. This review collected for each study: design, intervention, immune inclusion criteria, outcome, definition of sepsis, and source of infection. From the 80 studies assessed for eligibility, 29 were included: 17 RCT, 6 observational prospective studies, 6 ongoing RCT. Sepsis was defined based upon current recommendations at the time, with most patients presenting at least one organ failure. We found important heterogeneity regarding the use of immune parameters, both as inclusion and as outcome criteria. Only 13 studies selected patients suffering from immunosuppression based on immune biomarkers. Two immune criterias were commonly used: lymphocyte count and monocytic HLA-DR expression. This heterogeneity criteria in studies targeting SIS justify the conduct of a consensus process to define criteria to diagnose SIS and identify relevant outcomes markers.