Harnessing innate immune pathways for therapeutic advancement in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 25, 2024

Abstract The innate immune pathway is receiving increasing attention in cancer therapy. This ubiquitous across various cell types, not only cells but also adaptive cells, tumor and stromal cells. Agonists targeting the have shown profound changes microenvironment (TME) improved prognosis preclinical studies. However, to date, clinical success of drugs remains limited. Interestingly, recent studies that activation can paradoxically promote progression. uncertainty surrounding therapeutic effectiveness targeted for a critical issue needs immediate investigation. In this review, we observe role demonstrates heterogeneity, linked development stage, status, specific types. We propose within TME, exhibits multidimensional diversity. diversity fundamentally rooted cellular heterogeneity manifested as variety signaling networks. pro-tumor effect essentially reflects suppression classical pathways potential alternative pathways. Refining our understanding tumor’s network employing appropriate strategies enhance ability harness anti-tumor ultimately bridge gap from application.

Language: Английский

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The Role of Oxidative Stress in Tumorigenesis and Progression

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 441 - 441

Published: March 2, 2024

Oxidative stress refers to the imbalance between production of reactive oxygen species (ROS) and endogenous antioxidant defense system. Its involvement in cell senescence, apoptosis, series diseases has been demonstrated. Advances carcinogenic research have revealed oxidative as a pivotal pathophysiological pathway tumorigenesis be involved lung cancer, glioma, hepatocellular carcinoma, leukemia, so on. This review combs effects on each phase fate determination, three features are discussed. takes part processes ranging from tumor death via pathways like mitochondrial stress, endoplasmic reticulum ferroptosis. It can affect by engaging complex relationships death, cancer. The influence progression is multi-stage interlaced process that includes two aspects promotion inhibition, with mitochondria core regulation. A deeper more comprehensive understanding conducive exploring therapies.

Language: Английский

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Rational Nanomedicine Design Enhances Clinically Physical Treatment‐Inspired or Combined Immunotherapy

Advanced Science, Journal Year: 2022, Volume and Issue: 9(29)

Published: Aug. 24, 2022

Independent of tumor type and non-invasive or minimally-invasive feature, current physical treatments including ultrasound therapy, microwave ablation (MWA), radiofrequency (RFA) are widely used as the local treatment methods in clinics for directly killing tumors activating systematic immune responses. However, activated responses inadequate incompetent recession, incomplete thermal even aggravates immunosuppressive microenvironment (ITM), resulting intractable recurrence metastasis. Intriguingly, nanomedicine provides a powerful platform they can elevate energy utilization efficiency augment oncolytic effects mitigating ITM potentiating Especially after combining with clinical immunotherapy, anti-tumor effect by enhancing human system is reached, enabling effective prevention against This review systematically introduces cutting-edge progress direction nanobiotechnologies their corresponding nanomaterials. Moreover, enhanced progression, relapse, metastasis via autologous immunity exogenous immunotherapeutic agents exemplified, rationales analyzed. offers general guidance directions to enhance from perspectives activation magnification.

Language: Английский

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Divergent functions of NLRP3 inflammasomes in cancer: a review

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 15, 2023

Abstract The cancer is a serious health problem, which death rate (cancer mortality) 158.3 per 100,000 men and women year (based on 2013–2017 deaths). Both clinical translational studies have demonstrated that chronic inflammation associated with Cancer progression. However, the precise mechanisms of inflammasome, pathways mediate this phenomenon are not fully characterized. One most recently identified signaling pathways, whose activation seems to affect many metabolic disorders, “inflammasome” multiprotein complex composed NLRP3 (nucleotide-binding domain leucine-rich repeat protein 3), ASC (apoptosis speck-like containing CARD), procaspase-1. inflammasome leads processing secretion proinflammatory cytokines interleukin-1β (IL-1β) IL-18. goal paper review new insights effects in crosstalk between different organs, for better understanding role pathogenesis. We will provide here perspective current research may represent an innovative therapeutic target reverse malignancy condition consequences inflammation.

Language: Английский

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Uncoupled pyroptosis and IL-1β secretion downstream of inflammasome signaling

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 6, 2023

Inflammasomes are supramolecular platforms that organize in response to various damage-associated molecular patterns and pathogen-associated patterns. Upon activation, inflammasome sensors (with or without the help of ASC) activate caspase-1 other inflammatory caspases cleave gasdermin D pro-IL-1β/pro-IL-18, leading pyroptosis mature cytokine secretion. Pyroptosis enables intracellular pathogen niche disruption content release at cost cell death, inducing pro-inflammatory responses neighboring cells. IL-1β is a potent regulator for neutrophil recruitment, macrophage T-cell expansion. Thus, secretion two main mechanisms occur downstream signaling; they maintain homeostasis, drive innate immune response, shape adaptive immunity. This review aims discuss possible mechanisms, timing, consequences, significance uncoupling preferences signaling. While may be usually coupled, pyroptosis-predominant cytokine-predominant also observed stimulus-, type-, context-dependent manner, contributing pathogenesis development numerous pathological conditions such as cryopyrin-associated periodic syndromes, LPS-induced sepsis, Salmonella enterica serovar Typhimurium infection. Hyperactive cells consistently LDH leakage pyroptotic thereby prolonged inflammation, expanding lifespans pyroptosis-resistant neutrophils, hyperactivating stimuli-challenged macrophages, dendritic cells, monocytes, specific nonimmune Death activation induces GSDMD-mediated with no secretion, which increase lethality vivo . The sublytic GSDMD pore formation associated lower expressions components, extracellular vesicles, GSDMD-independent pathways involve unconventional could contribute uncoupling; regulation dynamics, generate active species different activities terms pro-IL-1β, lead uncoupling. These enable precise reactions stimuli intensities under single-cell level, promoting cooperative host fate decisions participating “game”. Appropriate coupling required heal tissues eliminate threats, further studies exploring tilt toward helpful.

Language: Английский

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Mitochondrial DNA induces nucleus pulposus cell pyroptosis via the TLR9-NF-κB-NLRP3 axis

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: June 15, 2023

Nucleus pulposus cell (NPC) death and progressive reduction play important roles in intervertebral disc degeneration (IVDD). As part of a damage-associated molecular pattern, mitochondrial DNA (mtDNA) can be recognized by TLR9 triggers the expression NF-κB NLRP3 inflammasomes, inducing pyroptosis inflammatory response. However, whether mtDNA induces NPC via TLR9-NF-κB-NLRP3 axis promotes IVDD remains uncertain.We constructed an vitro oxidative stress injury model to clarify mechanism release, TLR9-NF-κB signaling pathway activation, injury. We further verified action underlying inhibition release or activation vitro. then rat punctured understand inhibiting IVDD.We used human NP specimen assays show that levels TLR9, NF-κB, inflammasomes correlated with degree IVDD. demonstrated mediated stress-induced Oxidative damage mitochondria NPCs, causing opening permeability transition pores (mPTP) leading into cytosol. Furthermore, mPTP blocked thereby IVDD.mtDNA plays key role mediating axis. Our findings provide new potential targets for

Language: Английский

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Oxidative Stress and Potential Antioxidant Therapies in Vitiligo: A Narrative Review

Molecular Diagnosis & Therapy, Journal Year: 2023, Volume and Issue: 27(6), P. 723 - 739

Published: Sept. 22, 2023

Vitiligo is a chronic skin disorder characterised by the loss of melanocytes and subsequent depigmentation. Although many theories have been proposed in literature, none alone explains pathogenesis vitiligo. Oxidative stress has identified as potential factor A growing body evidence suggests that antioxidant therapies may offer promising approach to managing this condition. This review summarises mechanisms oxidative types melanocyte death We also provide brief overview most commonly studied antioxidants. Melanocytes vitiligo are thought be damaged an accumulation reactive oxygen species destroy structural functional integrity their DNA, lipids, proteins. Various causes, including exogenous endogenous factors, imbalance between prooxidants antioxidants, disruption pathways, gene polymorphisms, lead overproduction species. necroptosis, pyroptosis, ferroptosis, oxeiptosis newer cell contribute pathophysiology vitiligo, apoptosis remains mechanism According studies, vitamin E helps treat lipid peroxidation caused psoralen ultra-violet treatment. In addition, Polypodium leucotomos increased efficacy or narrow-band ultraviolet B therapy. Our provides valuable insights into role antioxidant-based supporting treating offering avenue for further research development effective treatment strategies.

Language: Английский

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Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 30, 2024

In the realm of cancer research, tumor microenvironment (TME) plays a crucial role in initiation and progression, shaped by complex interactions between cells surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted various cellular constituents within TME, including immune cells, cancer-associated fibroblasts, themselves. These cytokines facilitate intricate communication networks that significantly influence initiation, metastasis, suppression. Pyroptosis contributes to TME remodeling promoting release pro-inflammatory sustaining chronic inflammation, impacting processes such escape angiogenesis. However, challenges remain due interplay among cytokines, pyroptosis, along with dual effects pyroptosis on progression therapy-related complications like cytokine syndrome. Unraveling these complexities could strategies balance inflammatory responses while minimizing tissue damage during therapy. This review delves into crosstalk elucidating their contribution metastasis. By synthesizing emerging therapeutic targets innovative technologies concerning this aims provide novel insights enhance treatment outcomes for patients.

Language: Английский

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Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: June 6, 2024

Background The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether TyG is of prevalent cancer women. Methods cross-sectional included 142,184 women from REACTION (Risk Evaluation Cancers Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older 25 centers across mainland China between 2011 and 2012. was calculated according formula: Ln (fasting triglycerides [mg/dL] × fasting [mg/dL]/2). Multivariable-adjusted logistic regression models were used evaluate odds ratios (ORs) 95% confidence intervals (CIs) regarding associations Results analysis showed that compared lowest quartile index, highest significantly cancer, OR (95% CI) 1.61 (1.19–2.17). In stratified analysis, each 1 SD increase more dominant individuals menarche at age 13–17, those who postmenopausal, a history breastfeeding, had two four children, ORs CIs) 1.35 (1.09–1.68), 1.27 (1.05–1.54), 1.26 (1.05–1.52), 1.32 (1.08–1.62), respectively. Moreover, without discernible insulin resistance (homeostatic model assessment-insulin [HOMA-IR] ≥2.5), hyperglycemia dyslipidemia, 1.36-fold risk, 2.36 (1.44–3.87). Conclusion middle-aged elderly

Language: Английский

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Let’s make it personal: CRISPR tools in manipulating cell death pathways for cancer treatment

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: July 29, 2024

Abstract Advancements in the CRISPR technology, a game-changer experimental research, have revolutionized various fields of life sciences and more profoundly, cancer research. Cell death pathways are among most deregulated cells considered as critical aspects development. Through decades, our knowledge mechanisms orchestrating programmed cellular has increased substantially, attributed to revolution cutting-edge technologies. The heroic appearance systems expanded available screening platform genome engineering toolbox detect mutations create precise edits. In that context, ability this system for identification targeting cell signaling result development therapy resistance is an auspicious choice transform accelerate individualized therapy. concept personalized stands on molecular characterization individual tumor its microenvironment order provide treatment with highest possible outcome minimum toxicity. This study explored potential technology precision by identifying specific pathways. It showed promise finding key components involved death, making it tool targeted However, also highlighted challenges limitations need be addressed future research fully realize treatment. Graphical abstract Current application through glance. A choosing appropriate biological model vitro (using established lines, animal derived cells, human stem or T cells), vivo models which can harbor tumor), ex (human/animal-derived organoids). B preparation gRNA library. C design screening, desired gRNAs phenotypic response. D CRISPR-Cas identified targets, Cas9 gene editing (Knockout, base editing, prime editing), RNA modulation (modulation splicing, interference), epigenomic edits interference/activation using dead (dCas9) (Bock et al. 2022b)

Language: Английский

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