Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

OncoImmunology, Journal Year: 2020, Volume and Issue: 9(1)

Published: Jan. 1, 2020

The term ‘immunogenic cell death’ (ICD) denotes an immunologically unique type of regulated death that enables, rather than suppresses, T cell-driven immune responses are specific for antigens derived from the dying cells. ability ICD to elicit adaptive immunity heavily relies on immunogenicity cells, implying such cells must encode and present not covered by central tolerance (antigenicity), deliver immunostimulatory molecules as damage-associated molecular patterns cytokines (adjuvanticity). Moreover, host system be equipped detect antigenicity adjuvanticity As cancer (but normal) express several tolerance, they can driven into some therapeutic agents, including limited to) chemotherapeutics anthracycline family, oxaliplatin bortezomib, well radiation therapy. In this Trial Watch, we describe current trends in preclinical clinical development ICD-eliciting chemotherapy partner immunotherapy, with a focus trials assessing efficacy context immunomonitoring.

Language: Английский

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Traumatic Brain Injury: Mechanisms of Glial Response

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 22, 2021

Traumatic brain injury (TBI) is a heterogeneous disorder that involves damage due to external forces. TBI the main factor of death and morbidity in young males with high incidence worldwide. causes central nervous system (CNS) under variety mechanisms, including synaptic dysfunction, protein aggregation, mitochondrial oxidative stress, neuroinflammation. Glial cells comprise most CNS, which are mediators brain’s response TBI. In CNS present astrocytes, microglia, oligodendrocytes, polydendrocytes (NG2 cells). Astrocytes play critical roles ion water homeostasis, energy metabolism, blood-brain barrier, immune response. TBI, astrocytes change their morphology expression. Microglia primary phagocytic activity. After microglia also release both pro anti-inflammatory mediators. Oligodendrocytes myelin producers promoting axonal support. oligodendrocyte apoptosis, demyelination, transport disruption. There various interactions between these glial neurons contribute pathophysiology this review, we summarize several hallmarks relevant for understanding neuronal conditions.

Language: Английский

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The Immune and Regenerative Response to Burn Injury

Cells, Journal Year: 2022, Volume and Issue: 11(19), P. 3073 - 3073

Published: Sept. 29, 2022

Burn are diverse and complex injuries that not only have local effects but also serious systemic consequences through severe prolonged inflammatory response. They caused by heat, electricity, friction, chemicals, or radiation commonly divided into superficial, superficial partial-, deep partial- full-thickness injuries. The severity of the burn depends mainly on size depth injury location, age, underlying diseases. A strong immune response makes major burns even worse causing multiple including damage to heart, lungs, blood vessels, kidneys, other organs. Burns do require surgical excision, partial-thickness, follow known progression wound healing (inflammation, proliferation, remodeling), whilst full thickness requiring excision grafting not. For these burns, intervention is required for optimal coverage, function, cosmesis. Annually millions people worldwide suffer from associated with high morbidity mortality. Fortunately, over past decades, care has significantly improved. improvement in understanding pathophysiology led developments skin grafting, fluid resuscitation, infection control nutrition This review article focuses regenerative responses following injury. In Introduction, we describe epidemiology pathophysiology. focus chapter Next, define introducing all different cell types involved. Subsequently, discuss as well some emerging novel treatments battle against burns.

Language: Английский

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The Critical Roles and Mechanisms of Immune Cell Death in Sepsis

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 25, 2020

Sepsis was first described by the ancient Greek physicians over 2000 years ago. The pathophysiology of disease, however, is still not fully understood and hence mortality rate unacceptably high due to lack specific therapies. In last decade, great progress has been made shifting focus research from systemic immune response syndrome (SIRS) multiple organ dysfunction (MODS). re-defined as infection-induced MODS in 2016. How infection leads clear, but what mediates becomes major topic understanding molecular mechanisms developing Recently, mechanism extensive cell death which releases a large quantity damage-associated patterns (DAMPs) their roles development well immunosuppression during sepsis have attracted much attention. A growing amount evidence supports hypothesis that DAMPs, including high-mobility group box 1 protein (HMGB1), cell-free DNA (cfDNA) histones neutrophil extracellular traps (NETs), may directly or indirectly contribute significantly MODS. Here, we provide an overview consequences sepsis. We also propose pivotal pathway local eventual potential combined therapeutic strategy for targeting

Language: Английский

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The Impact of Acute or Chronic Alcohol Intake on the NF-κB Signaling Pathway in Alcohol-Related Liver Disease

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(24), P. 9407 - 9407

Published: Dec. 10, 2020

Ethanol misuse is frequently associated with a multitude of profound medical conditions, contributing to health-, individual- and social-related damage. A particularly dangerous threat from this classification coined as alcoholic liver disease (ALD), condition caused by prolonged alcohol overconsumption, involving several pathological stages induced metabolic byproducts sustained cellular intoxication. Molecular, mechanisms ALD principally root in the innate immunity system are especially enhanced functionality nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) pathway. NF-κB an interesting convoluted DNA transcription regulator, promoting both anti-inflammatory pro-inflammatory gene expression. Thus, abundancy studies recent years underlines importance inflammatory responses mechanistic stimulation inner molecular motifs within components. Hereby, following review, we would like put emphasis on correlation between inflammation signaling pathway progression. We will provide reader current knowledge regarding chronic acute consumption patterns, development, involvement its enzymatic regulators. Therefore, review various experimental vitro vivo research ALD, including active compound treatments genetic modification approach. Furthermore, our investigation covers few human studies.

Language: Английский

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Secondary immunodeficiencies

Annals of Allergy Asthma & Immunology, Journal Year: 2021, Volume and Issue: 127(6), P. 617 - 626

Published: Sept. 3, 2021

Language: Английский

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Role of DAMPs in respiratory virus-induced acute respiratory distress syndrome—with a preliminary reference to SARS-CoV-2 pneumonia

Genes and Immunity, Journal Year: 2021, Volume and Issue: 22(3), P. 141 - 160

Published: June 17, 2021

When surveying the current literature on COVID-19, "cytokine storm" is considered to be pathogenetically involved in its severe outcomes such as acute respiratory distress syndrome, systemic inflammatory response and eventually multiple organ failure. In this review, similar role of DAMPs addressed, that is, those molecules, which operate upstream pathway by activating cells, ultimately release cytokines. Given still limited reports their emerging topic extended viral infections with focus influenza. At first, a brief introduction given function various classes counterbalancing suppressing (SAMPs) initiating controlled inflammation-promoting inflammation-resolving defense responses upon infectious sterile insults. It stressed excessive emission injury uncovers fateful property triggering dysregulated life-threatening hyperinflammatory responses. Such scenario may happen when load too high, for example, tract, "forcing" many virus-infected host cells decide commit "suicidal" regulated cell death (e.g., necroptosis, pyroptosis) associated large amounts DAMPs: an important review. Ironically, although aim save restore organismal homeostasis, intrinsic leads responses—as typically pathogenesis syndrome infections. Consequently, briefly outlined these molecules can valuable diagnostic prognostic biomarkers monitor evaluate course disorder, particular, grasp eventual transition precociously from observed mild/moderate cases seen, severe/fatal COVID-19. Moreover, pathogenetic involvement qualifies them relevant future therapeutic targets prevent severe/ fatal outcomes. Finally, theory presented proposing superimposition coronavirus-induced non-virus-induced other origins air pollution or high age contribute courses coronavirus pneumonia.

Language: Английский

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An Injectable Antibiotic Hydrogel that Scavenges Proinflammatory Factors for the Treatment of Severe Abdominal Trauma

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(27)

Published: April 7, 2022

Abstract Bacterial infection and excessive inflammation following abdominal injury can cause life‐threatening complications that lead to multiple organ failure death. Removing bacteria proinflammatory factors—which are predominantly negatively charged—from the wound site with a cationic, antibiotic‐containing hydrogel dressing is therefore promising treatment approach for severe trauma. Here an injectable, self‐healing composed of gel‐forming glycosaminoglycan oxidized chondroitin sulfate (OCS), cationic polyethylenimine (PEI), antibiotic tobramycin (Tob) via Schiff's base reaction developed. Compared hydrogels lacking either PEI or Tob, only Tob/PEI/OCS exhibit large binding capacity negatively‐charged factors including cell‐free DNA, lipopolysaccharides, TNF‐α, high mobility group box 1 protein, reduction in bacterial populations vitro. In murine model trauma, exhibits good biodegradability biosafety, reduced local systemic infection, prevents failure, resulting 100% survival. This thus biomaterial preventing improving outcomes

Language: Английский

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Properties and Application of Cell-Free DNA as a Clinical Biomarker

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(17), P. 9110 - 9110

Published: Aug. 24, 2021

Biomarkers are valuable tools in clinical practice. In 2001, the National Institutes of Health (NIH) standardized definition a biomarker as characteristic that is objectively measured and evaluated an indicator normal biological processes, pathogenic or pharmacological responses to therapeutic intervention. A has relevance when it presents precision, standardization reproducibility, suitability patient, straightforward interpretation by clinicians, high sensitivity and/or specificity parameter proposes identify. Thus, serum biomarkers should have advantages related simplicity procedures fact venous blood collection commonplace We described potentiality cfDNA general focused on endothelial dysfunction. Circulating cell-free DNA (cfDNA) refers extracellular present body fluid may be derived from both diseased cells. An increasing number studies demonstrate potential use noninvasive determine physiologic pathologic conditions. However, although still scarce, evidence been reported regarding using cardiovascular diseases. Here, we reviewed history cfDNA, its source, molecular features, release mechanism. also show recent investigated possible marker damage settings. system, quite new, interesting, stronger needed. some drawbacks methodologies overcome before recommendation setting.

Language: Английский

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Postoperative systemic inflammatory dysregulation and corticosteroids: a narrative review

Anaesthesia, Journal Year: 2022, Volume and Issue: 78(3), P. 356 - 370

Published: Oct. 29, 2022

In some patients, the inflammatory-immune response to surgical injury progresses a harmful, dysregulated state. We posit that postoperative systemic inflammatory dysregulation forms part of pathophysiological places patients at increased risk complications and subsequently prolongs hospital stay. this narrative review, we have outlined evolution, measurement prediction dysregulation, distinguishing it from healthy self-limiting host response. reviewed actions glucocorticoids potential for heterogeneous responses peri-operative corticosteroid supplementation. then appraised evidence highlighting safety supplementation, benefits high/repeated doses reduce risks major death. Finally, addressed how clinical trials in future should target higher complications, whereby regimes be tailored modify not only priori risk, but also further adjusted markers an evolving

Language: Английский

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