Current status of immunomodulatory therapies in adult sepsis patients: where do we stand?

INTRODUCTION: Despite advances, sepsis remains a leading cause of morbidity and mortality worldwide. Dysregulated host responses are known to characterize sepsis, and while numerous clinical trials using immunomodulatory strategies have been attempted, most fail to show benefit. An important reason for their failure can be attributed to the heterogeneity of the host immune responses. Based on improvements in endotype characterization, personalized precision immunotherapy approaches now show promise.

AREAS COVERED: This review covers personalized approaches to sepsis, with a focus on the use of biomarker-guided immunomodulatory treatments. A literature search of clinical trials on sepsis immunomodulatory therapies was conducted using the PubMed database. Ongoing clinical trials on sepsis immunomodulation were also identified and reviewed.

EXPERT OPINION: Precision immunotherapy may represent the next step in sepsis management. Recent breakthrough studies have led to the identification of biomarkers that classify patients into distinct endotypes and predict response to treatment. These biomarkers need to guide us through the proper selection of patients, the timely initiation and cessation of treatment, and sometimes even the adaptation to another endotype. The integration of serial immune monitoring, adaptive clinical trial designs, and endotype-specific treatment algorithms has the potential to move the field forward.