Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis.
Publication/Presentation Date
2-4-2020
Abstract
BACKGROUND: Animal studies reporting immune checkpoint inhibitors (CPIs) improved host defense and survival during bacterial sepsis provided one basis for phase I CPI sepsis trials. We performed a systematic review and meta-analysis examining the benefit of CPI therapy in preclinical studies, and whether variables potentially altering this clinical benefit were investigated. Studies were analyzed that compared survival following bacteria or lipopolysaccharide challenge in animals treated with inhibitors to programmed death-1 (PD-1), PD-ligand1 (PD-L1), cytotoxic T lymphocyte-associated protein-4 (CTLA-4), or B- and T-lymphocyte attenuator (BTLA) versus control.
RESULTS: Nineteen experiments from 11 studies (n = 709) were included. All experiments were in mice, and 10 of the 19 were published from a single research group. Sample size calculations and randomization were not reported in any studies, and blinding procedures were reported in just 1. Across all 19 experiments, CPIs increased the odds ratio for survival (OR, 95% CI) [3.37(1. 55, 7.31)] but with heterogeneity (I
CONCLUSIONS: Preclinical studies showing that CPIs add benefit to antibiotic therapy for the common bacterial infections causing sepsis clinically are needed to support this therapeutic approach. Studies should be reproducible across multiple laboratories and include procedures to reduce the risk of bias.
Volume
8
Issue
1
First Page
7
Last Page
7
ISSN
2197-425X
Published In/Presented At
Busch, L. M., Sun, J., Cui, X., Eichacker, P. Q., & Torabi-Parizi, P. (2020). Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis. Intensive care medicine experimental, 8(1), 7. https://doi.org/10.1186/s40635-019-0290-x
Disciplines
Medicine and Health Sciences
PubMedID
32020483
Department(s)
Department of Medicine
Document Type
Article