Immune Endotype-Guided Precision Immunotherapy in Sepsis: From Transcriptomics to Bedside Application

Abstract

Sepsis is a life-threatening syndrome characterized by profound biological heterogeneity and dynamic immune dysregulation. Traditional uniform treatment strategies have failed to account for distinct immune endotypes ranging from hyperinflammation to immunoparalysis. Advances in transcriptomic, proteomic, and cellular profiling have enabled the identification of reproducible immune phenotypes with differing prognoses and therapeutic responsiveness. Hyperinflammatory states may benefit from targeted cytokine inhibition, whereas immunosuppressed phenotypes marked by reduced monocyte HLA-DR (human leukocyte antigen-DR) expression, lymphopenia, and T-cell exhaustion may require immunostimulatory therapies such as GM-CSF (granulocyte-colony stimulating factor), interferon-γ, or interleukin-7. Emerging evidence suggests that aligning immunomodulatory interventions with the patient's prevailing immune profile could improve outcomes and avoid harm associated with non-stratified therapy. This study was conducted as a structured narrative scoping review, with a comprehensive literature search of PubMed/MEDLINE, Embase, Scopus, and Web of Science covering publications from 2010 to 2025, using keywords related to sepsis, immune dysregulation, endotypes, biomarkers, and precision medicine. This review aims to examine the role of immune endotypes in the pathophysiology and clinical heterogeneity of sepsis and to evaluate emerging evidence on biomarker- and transcriptomic-guided precision immunotherapy. Implementation of precision medicine in sepsis depends on standardized endotyping tools, serial immune monitoring, and biomarker-enriched adaptive trial designs. Although logistical and translational barriers remain, immune-guided therapy represents a promising but unproven paradigm that requires rigorous prospective validation through adaptive, biomarker-enriched trials.