Sex differences in disease: sex chromosome and immunity

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 27, 2024

Abstract Sex is a fundamental biological variable that influences immune system function, with sex chromosomes (X and Y) playing central role in these differences. Despite substantial evidence of disparities responses between males females, biomedical research has historically overlooked as critical factor. This oversight contributed to the observed susceptibility autoimmune diseases, infectious malignancies sexes. In this review, we address phenomena mechanisms through which aberrant expression chromosome-linked genes contributes sex-based differences responses. We specifically focus on implications X chromosome inactivation (XCI) escape loss Y (LOY). Our review aims elucidate molecular driving differences, particular emphasis interactions cells both females. Additionally, discuss potential impact disease identify prospective therapeutic targets. As personalized precision medicine advances, it crucial integrate into immunological clinical trials. advocate for an increased considerations fundamental, translational, promote personalized, sex-specific healthcare.

Language: Английский

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The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 382 - 382

Published: Jan. 16, 2024

Sex is an important factor influencing the immune system, and distribution of tumors, including their types subtypes, characterized by sexual dichotomy. The aim this study was to investigate whether there association between sex treatment effect checkpoint inhibitors (ICI). Four bibliographic databases were searched. Studies randomized controlled trials (RCTs) assessing efficacy ICI identified used, primary endpoint difference in males females, presented as overall survival (OS), progression-free (PFS) recurrence-free (RFS). calculated pooled HRs 95% CIs for OS, PFS RFS females using a random effects model or fixed model, thereby assessed on treatment. This registered with PROSPERO (CRD42022370939). A total 103 articles, 63,755 patients cancer, retrieved from database, which approximately 70% males. In studies OS outcome, combined hazard ratio (HR) 0.77 (95% CI 0.74-0.79) male treated 0.81 0.78-0.85) female compared controls, respectively. significant. therapy, under suitable conditions its use, has positive impact various benefit more than females. It may be necessary develop different tumor immunotherapy strategies sexes.

Language: Английский

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Potential mechanisms of cancer stem‐like progenitor T‐cell bio‐behaviours

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(8)

Published: Aug. 1, 2024

In situations involving continuous exposure to antigens, such as chronic infections or cancer, antigen-specific CD8

Language: Английский

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NOTCH1 drives sexually dimorphic immune responses in hepatocellular carcinoma

Cancer Discovery, Journal Year: 2024, Volume and Issue: 15(3), P. 495 - 510

Published: Nov. 19, 2024

Hepatocellular carcinoma presents strong sexual dimorphism, being two to three times more frequent in males than females; however, the role of sex response immunotherapies HCC remains unknown. We demonstrate that NOTCH1, an understudied oncogene HCC, elicits sexually dimorphic antitumor immunity and FDA-approved immunotherapies. Surprisingly, harboring NOTCH1-driven tumors displayed enhanced immune responses, which, mice, were mediated by dendritic T cells. Conversely, females presented evasion resistance through a defect cell (DC)-mediated priming activation CD8+ cells which was restored therapeutically with CD40 agonism. Mechanistically, genes chromosomes but not hormones. Together, our study unravels unexpected association between NOTCH1 cancer highlights potential restoring DC-CD8+ T-cell axis agonism improve outcomes. Significance: Although elusive. With novel mouse model validation patients we disrupts specifically mechanism chromosome genes, is reversed See related commentary Zhu Koltsova, p. 452.

Language: Английский

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Ibrutinib disrupts blood-tumor barrier integrity and prolongs survival in rodent glioma model

Acta Neuropathologica Communications, Journal Year: 2024, Volume and Issue: 12(1)

Published: April 8, 2024

Abstract In malignant glioma, cytotoxic drugs are often inhibited from accessing the tumor site due to blood-tumor barrier (BTB). Ibrutinib, FDA-approved lymphoma agent, inhibits Bruton tyrosine kinase (BTK) and has previously been shown independently impair aortic endothelial adhesion increase rodent glioma model survival in combination with therapy. Yet additional research is required understand ibrutinib’s effect on BTB function. this study, we detail baseline BTK expression cells its surrounding vasculature, then measure junctional expression/function changes varied ibrutinib doses vitro. Rat models were treated alone (1–10 µM 25 mg/kg) doxil (10–100 3 assess additive effects viability, drug concentrations, volume, survival. We found that ibrutinib, a dose-dependent manner, decreased brain cell–cell over 24 h, without affecting cell viability ( p < 0.005). Expression of tight junction gene protein was maximally 4 h after administration, along inhibition efflux transporter, ABCB1, activity. demonstrated an rat cells, as seen by significant reduction 0.001) increased CNS concentration (56 ng/mL vs. 74.6 combination, 0.05). Finally, combined doxil, prolonged median (27 16 days, 0.0001) imaging showing − 53% versus 75% volume change therapy These findings indicate ability permeability via disruption inhibition, entry prolong Our results motivate need identify other modifiers, all intent improving reducing systemic toxicities.

Language: Английский

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