• Marleen A Slim, Niels van Mourik, Lieke Bakkerus, Katherine Fuller, Lydia Acharya, Tatiana Giannidis, Joanna C Dionne, OczkowskiSimon J WSJWDepartment of Medicine, McMaster University, Hamilton, Canada.The Guidelines in Intensive Care Development and Evaluation (GUIDE) Group, Research Institute St. Joseph's Healthcare Hamilton, Hamilton, Canada.Department of Health Resear, Mihai G Netea, Peter Pickkers, Evangelos J Giamarellos-Bourboulis, MüllerMarcella C AMCADepartment of Intensive Care Medicine, Amsterdam University Medical Center, Meibergdreef 9, Room G3-220, 1105 AZ, Amsterdam, The Netherlands., Tom van der Poll, W Joost Wiersinga, ImmunoSep Consortium, VlaarAlexander P JAPJDepartment of Intensive Care Medicine, Amsterdam University Medical Center, Meibergdreef 9, Room G3-220, 1105 AZ, Amsterdam, The Netherlands., and Lonneke A van Vught.
• Department of Intensive Care Medicine, Amsterdam University Medical Center, Meibergdreef 9, Room G3-220, 1105 AZ, Amsterdam, The Netherlands. m.a.slim@amsterdamumc.nl.
• Crit Care. 2024 May 28; 28 (1): 183183.

AbstractDespite significant progress in our understanding of the pathophysiology of sepsis and extensive clinical research, there are few proven therapies addressing the underlying immune dysregulation of this life-threatening condition. The aim of this scoping review is to describe the literature evaluating immunotherapy in adult patients with sepsis, emphasizing on methods providing a "personalized immunotherapy" approach, which was defined as the classification of patients into a distinct subgroup or subphenotype, in which a patient's immune profile is used to guide treatment. Subgroups are subsets of sepsis patients, based on any cut-off in a variable. Subphenotypes are subgroups that can be reliably discriminated from other subgroup based on data-driven assessments. Included studies were randomized controlled trials and cohort studies investigating immunomodulatory therapies in adults with sepsis. Studies were identified by searching PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov, from the first paper available until January 29th, 2024. The search resulted in 15,853 studies. Title and abstract screening resulted in 1409 studies (9%), assessed for eligibility; 771 studies were included, of which 282 (37%) were observational and 489 (63%) interventional. Treatment groups included were treatments targeting the innate immune response, the complement system, coagulation and endothelial dysfunction, non-pharmalogical treatment, pleiotropic drugs, immunonutrition, concomitant treatments, Traditional Chinese Medicine, immunostimulatory cytokines and growth factors, intravenous immunoglobulins, mesenchymal stem cells and immune-checkpoint inhibitors. A personalized approach was incorporated in 70 studies (9%). Enrichment was applied using cut-offs in temperature, laboratory, biomarker or genetic variables. Trials often showed conflicting results, possibly due to the lack of patient stratification or the potential influence of severity and timing on immunomodulatory therapy results. When a personalized approach was applied, trends of clinical benefit for several interventions emerged, which hold promise for future clinical trials using personalized immunotherapy.© 2024. The Author(s).

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