ReviewFrontiers in immunology2022
The Neonatal Innate Immune Response to Sepsis: Checkpoint Proteins as Novel Mediators of This Response and as Possible Therapeutic/Diagnostic Levers.
Review in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Using molecular methods to diagnose, classify, and treat neonatal sepsis: a scoping review.Frontiers in pediatrics · 2025Pooled it
- Serum Soluble Programmed Death Ligand-1 (sPD-L1) as a Diagnostic Marker in Neonatal Sepsis.Indian journal of pediatrics · 2026Observational
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Factors Associated with Severe Respiratory Support Requirement in Neonates with Gram-Negative Infections: A Retrospective Cohort Study.Journal of clinical medicine · 2026Article
- Multi-omics insights into immunometabolic dysregulation in neonatal sepsis for precision medicine.Molecular biology reports · 2026Review
- Age-related differences and common pathways of lymphocyte subsets in sepsis: a comparative review of elderly and pediatric patients.Cell death & disease · 2026Review
- Proteomic biomarkers for early diagnosis and prognosis in pediatric sepsis.World journal of clinical pediatrics · 2026Article
- Pediatric Sepsis: Evolving Subphenotypes, Overlap Syndromes, and the Path to Precision Therapies.Clinics in chest medicine · 2026Review
- Exploratory Analysis of TLR2, TLR4, Interleukin 6 and Interleukin 10 Gene Polymorphisms in Relation to Clinical Early-Onset Sepsis in Preterm Neonates: A Single-Center Study.Life (Basel, Switzerland) · 2026Article
- Targeting VISTA for immunomodulation in sepsis: mechanisms and therapeutic potentials.Frontiers in immunology · 2026Review
- Thirty-five years of evolving inflammatory paradigms in sepsis (1991-2025): a comprehensive mapping of immune dysregulation research, anti-inflammatory targets, and translational barriers.Frontiers in immunology · 2026Article
- Mechanisms of immune suppression in sepsis/shock: one investigator's/lab group's experience (SLB 2024 legacy award presentation).Journal of leukocyte biology · 2025Article
- Molecular Mechanisms Underlying Inflammation in Early-Onset Neonatal Sepsis: A Systematic Review of Human Studies.Journal of clinical medicine · 2025Review
- Adenosine accumulation in the blood of newborn mice weakens antimicrobial host defenses.Journal of leukocyte biology · 2025Article
- Advancing Understanding ofMicroorganisms · 2025Article
- The progress of organ protection mechanisms in sepsis.Frontiers in immunology · 2025Review
- Immunomodulatory therapy for sepsis: from pathophysiological mechanisms to precision treatment.Frontiers in cellular and infection microbiology · 2025Review
- Neonatal Sepsis: Aetiology, Pathophysiology, Diagnostic Advances and Management Strategies.Clinical medicine insights. Pediatrics · 2024Review
- Review
- Immune Dysfunction-Associated Elevated RDW, APACHE-II, and SOFA Scores Were a Possible Cause of 28-Day Mortality in Sepsis Patients.Infection and drug resistance · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Sepsis, a dysfunctional immune response to infection leading to life-threatening organ injury, represents a significant global health issue. Neonatal sepsis is disproportionately prevalent and has a cost burden of 2-3 times that of adult patients. Despite this, no widely accepted definition for neonatal sepsis or recommendations for management exist and those created for pediatric patients are significantly limited in their applicability to this unique population. This is in part due to neonates' reliance on an innate immune response (which is developmentally more prominent in the neonate than the immature adaptive immune response) carried out by dysfunctional immune cells, including neutrophils, antigen-presenting cells such as macrophages/monocytes, dendritic cells, etc., natural killer cells, and innate lymphoid regulatory cell sub-sets like iNKT cells, γδ T-cells, etc. Immune checkpoint inhibitors are a family of proteins with primarily suppressive/inhibitory effects on immune and tumor cells and allow for the maintenance of self-tolerance. During sepsis, these proteins are often upregulated and are thought to contribute to the long-term immunosuppression seen in adult patients. Several drugs targeting checkpoint inhibitors, including PD-1 and PD-L1, have been developed and approved for the treatment of various cancers, but no such therapeutics have been approved for the management of sepsis. In this review, we will comparatively discuss the role of several checkpoint inhibitor proteins, including PD-1, PD-L1, VISTA, and HVEM, in the immune response to sepsis in both adults and neonates, as well as posit how they may uniquely propagate their actions through the neonatal innate immune response. We will also consider the possibility of leveraging these proteins in the clinical setting as potential therapeutics/diagnostics that might aid in mitigating neonatal septic morbidity/mortality.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.