Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 11, 2025

Abstract The negatively charged aminophospholipid, phosphatidylserine (PS), is typically restricted to the inner leaflet of plasma membrane under normal, healthy physiological conditions. PS irreversibly externalized during apoptosis, where it serves as a signal for elimination by efferocytosis. also reversibly and transiently cell activation such platelet immune activation. These events associated with externalization are tightly controlled regulated flippases scramblases. Indeed, improper regulation results in thrombotic diseases Scott Syndrome, defect coagulation thrombin production, case efferocytosis, can result autoimmunity systemic lupus erythematosus (SLE) when PS-mediated apoptosis efferocytosis fails. perturbed cancer viral infection, whereby becomes persistently exposed on surface stressed diseased cells, which lead chronic thrombosis evasion. In this review, we summarize evidence dysregulation main focus biology pathogenic mechanisms evasion signaling PS, well discussion new therapeutic strategies aimed target PS. We posit that universal agnostic marker tissues, cancer, likely reflects intrinsic form escape. continued development targeting provides rationale their co-utility adjuvants checkpoint therapeutics.

Language: Английский

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The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: May 22, 2025

Abstract Immune system plays a crucial role in the physiological and pathological regulation of cardiovascular system. The exploration history milestones immune diseases (CVDs) have evolved from initial discovery chronic inflammation atherosclerosis to large-scale clinical studies confirming importance anti-inflammatory therapy treating CVDs. This progress has been facilitated by advancements various technological approaches, including multi-omics analysis (single-cell sequencing, spatial transcriptome et al.) significant improvements immunotherapy techniques such as chimeric antigen receptor (CAR)-T cell therapy. Both innate adaptive immunity holds pivotal CVDs, involving Toll-like (TLR) signaling pathway, nucleotide-binding oligomerization domain-containing proteins 1 2 (NOD1/2) inflammasome RNA DNA sensing well antibody-mediated complement-dependent systems. Meanwhile, responses are simultaneously regulated multi-level regulations epigenetics (DNA, RNA, protein) other key pathways interactions among cells, between cardiac or vascular cells. Remarkably, based on basic research system, also made pre-clinical immunotherapy. review provides an overview providing in-depth insights into highlighting impact Finally, we discuss strategies targeting translational implications

Language: Английский

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Cholesterol efflux protein, ABCA1, supports anti-cancer functions of myeloid immune cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

ABSTRACT Although immune therapy has seen significant advances, the majority of breast and other solid tumors do not respond or quickly develop de novo resistance. One factor driving resistance is highly suppressive myeloid cells (MCs) such as macrophages. Previous work established clinical links between cholesterol cancer outcome, that MC function can be regulated through disruption in metabolism. Thus, we screened for proteins were expressed MCs, involved homeostasis whose expression was associated with survival; identify efflux protein ABCA1. Preclinical studies revealed ABCA1 activity resulted increased anti-cancer functions macrophages: enhanced tumor infiltration, decreased angiogenic potential, reduced efferocytosis, improved support CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, both PI3K dependent independent mechanisms. Assessment human blood correlations macrophages VEGFA , CD8 abundance activity, highlighting relevance our findings. The culmination effects on demonstrated growth metastasis mice specific knockout Therefore, modulating within MCs may represent a novel approach to therapy.

Language: Английский

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The role of SLC7A11 in diabetic wound healing: novel insights and new therapeutic strategies

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

Published: Sept. 3, 2024

Diabetic wounds are a severe complication of diabetes, characterized by persistent, non-healing ulcers due to disrupted wound-healing mechanisms in hyperglycemic environment. Key factors the pathogenesis these chronic include unresolved inflammation and antioxidant defense imbalances. The cystine/glutamate antiporter SLC7A11 (xCT) is crucial for cystine import, glutathione production, protection, positioning it as vital regulator diabetic wound healing. Recent studies underscore role modulating immune responses oxidative stress wounds. Moreover, influences critical processes such insulin secretion mTOR signaling pathway, both which implicated delayed This review explores regulating its impact on response, defenses, secretion, pathways Additionally, we highlight current advancements targeting treating related diseases conceptualize potential applications value treatment strategies, along with challenges encountered this context.

Language: Английский

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