Towards personalized medicine: a scoping review of immunotherapy in sepsis
Authors: Slim Marleen A. , van Mourik Niels , Bakkerus Lieke , Fuller Katherine , Acharya Lydia , Giannidis Tatiana , Dionne Joanna C. , Oczkowski Simon J. W. , Netea Mihai G. , Pickkers Peter , Giamarellos-Bourboulis Evangelos J. , Müller Marcella C. A. , van der Poll Tom , Wiersinga W. Joost ,   in collaboration with the ImmunoSep Consortium, Kullberg Bart-Jan , Nooijer Aline , Veerdonk Frank , Oever Jaap , Hoogerwerf Jacobien , Hulscher Marlies , Netea Mihai , Oerlemans Anke , Ziogas Athanasios , Swillens Julie , Berg Lisa , Bos Nynke , Kox Matthijs , Estratiou Leda , Giamarellos-Bourboulis Evangelos , Kotsaki Antigoni , Nikolaos Antonakos , Spyros Gregoriadis , Calandra Thierry , Meylan Sylvain , Snaka Tiia , Roger Thierry , Bauer Michael , Brunkhorst Frank , Bloos Frank , Weis Sebastian , Hartman Willy , Slim Marleen , Vught Lonneke , Vlaar Alexander , Muller Marcela , Wiersinga Joost , Lupse Mihaela , Santamarean Grigore , Rimmele Thomas , Conti Filippo , Monneret Guillaume , Aschenbrenner Anna , Schultze Joachim , Uelft Martina , Bock Christoph , terHorst Robert , Gat-Viks Irit , Ron Einat , Yunkovitz Gal , Ablott Sophie , Peronnet Estelle , Balezeaux Margaux , Saliou Adrien , Hart Julie , Vlaar Alexander P. J. , van Vught Lonneke A. 
Published: May 2024

Despite 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.