Reprogramming cellular senescence in the tumor microenvironment augments cancer immunotherapy through multifunctional nanocrystals DOI Creative Commons
Zheng Wang,

Yinglu Chen,

Hui Fang

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(44)

Published: Nov. 1, 2024

Harnessing the immunogenic potential of senescent tumor cells provides an opportunity to remodel microenvironment (TME) and boost antitumor immunity. However, this needs be sophisticatedly wielded avoid additional immunosuppressive capacity cells. Our study shows that blocking JAK2/STAT3 pathway enhances efficacy Aurora kinase inhibitor alisertib (Ali)-induced senescence by reducing senescence-associated secretory phenotype (SASP) while preserving SASP. Hypothesizing SASP reprogramming with Ali JAK2 ruxolitinib (Rux) will benefit cancer immunotherapy, we create nanoparticulate crystals (Ali-Rux) composed Rux a fully active pharmaceutical ingredient. Immunization Ali-Rux-orchestrated promotes stronger activation antigen-presenting cells, enhancing immune surveillance. This approach remodels TME increasing CD8

Language: Английский

Cellular senescence and SASP in tumor progression and therapeutic opportunities DOI Creative Commons

Zening Dong,

Yahan Luo,

Zhangchen Yuan

et al.

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

Published: Aug. 31, 2024

Cellular senescence (CS), a permanent and irreversible arrest of the cell cycle proliferation leading to degeneration cellular structure function, has been implicated in various key physiological pathological processes, particularly cancer. Initially, CS was recognized as barrier tumorigenesis, serving an intrinsic defense mechanism protect cells from malignant transformation. However, increasing evidence suggests that senescent can promote tumor progression overt malignancy, primarily through set factors known senescence-associated secretory phenotypes (SASPs), including chemokines, growth factors, cytokines, stromal metalloproteinases. These significantly reshape microenvironment (TME), enabling tumors evade immune destruction. Interestingly, some studies have also suggested SASPs may impede development by enhancing immunosurveillance. opposing roles highlight complexity heterogeneity diverse cancers. Consequently, there growing interest pharmacological interventions targeting or cancer therapy, such senolytics senomorphics, either clearance mitigate harmful effects SASPs. In this review, we will interpret concept CS, delve into role reshaping TME, summarize recent advances anti-tumor strategies

Language: Английский

Citations

38
Lactate and lactylation in cancer DOI Creative Commons
Jie Chen, Ziyue Huang,

Ya Chen

et al.

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

Published: Feb. 11, 2025

Abstract Accumulated evidence has implicated the diverse and substantial influence of lactate on cellular differentiation fate regulation in physiological pathological settings, particularly intricate conditions such as cancer. Specifically, been demonstrated to be pivotal molding tumor microenvironment (TME) through its effects different cell populations. Within cells, impacts signaling pathways, augments shuttle process, boosts resistance oxidative stress, contributes lactylation. In various populations, interplay between immune cells governs processes differentiation, response, surveillance, treatment effectiveness. Furthermore, communication stromal/endothelial supports basal membrane (BM) remodeling, epithelial-mesenchymal transitions (EMT), metabolic reprogramming, angiogenesis, drug resistance. Focusing production transport, specifically dehydrogenase (LDH) monocarboxylate transporters (MCT), shown promise Inhibitors targeting LDH MCT act both suppressors enhancers immunotherapy, leading a synergistic therapeutic effect when combined with immunotherapy. The review underscores importance progression provides valuable perspectives potential approaches that target vulnerability metabolism, highlighting Heel Achilles for cancer treatment.

Language: Английский

Citations

12
Modulation of the Neuro–Cancer Connection by Metabolites of Gut Microbiota DOI Creative Commons
Alice Njolke Mafe, Dietrich Büsselberg

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 270 - 270

Published: Feb. 12, 2025

The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, cancer progression. Recent advances have accentuated significant role of microbiota metabolites in modulating systemic processes that influence both brain health tumorigenesis. This paper explores emerging concept metabolite-mediated modulation within connection, focusing on key such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, lipopolysaccharides (LPS). While microbiota's impact immune regulation, neuroinflammation, tumor development is well established, gaps remain grasping how specific contribute to neuro-cancer interactions. We discuss with potential implications for neurobiology cancer, indoles polyamines, which yet be extensively studied. Furthermore, we review preclinical clinical evidence linking dysbiosis, altered metabolite profiles, tumors, showcasing limitations research gaps, particularly human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal transplantation, probiotics, demonstrate promise but also indicate hurdles translating these findings therapies. concludes call standardized multi-omics approaches bi-directional frameworks integrating microbiome, neuroscience, oncology develop personalized therapeutic strategies patients.

Language: Английский

Citations

3
Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways DOI Creative Commons
Bowei Liu, Zhigang Peng, Hao Zhang

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 2, 2025

Cellular senescence, a stable state of cell cycle arrest induced by various stressors or genomic damage, is recognized as hallmark cancer. It exerts context-dependent dual role in cancer initiation and progression, functioning tumor suppressor promoter. The complexity senescence arises from its mechanistic diversity, potential reversibility, heterogeneity. A key mediator these effects the senescence-associated secretory phenotype (SASP), repertoire bioactive molecules that influence microenvironment (TME) remodeling, modulate behavior, contribute to therapeutic resistance. Given intricate biology, presents both challenges opportunities for intervention. Strategies targeting pathways, including senescence-inducing therapies senolytic approaches, offer promising avenues treatment. This review provides comprehensive analysis regulatory mechanisms governing cellular tumors. We also discuss emerging strategies highlighting novel opportunities. deeper understanding processes essential developing precision improving clinical outcomes.

Language: Английский

Citations

3
The Role of cGAS-STING in Remodeling the Tumor Immune Microenvironment Induced by Radiotherapy DOI
Qingyu Jiang,

Zhiheng Chen,

Jin Jiang

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: 209, P. 104658 - 104658

Published: Feb. 15, 2025

Language: Английский

Citations

2
Cellular senescence and wound healing in aged and diabetic skin DOI Creative Commons
Arisa Kita, Sena Yamamoto, Yuki Saito

et al.

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

Published: Feb. 19, 2024

Cellular senescence is a biological mechanism that prevents abnormal cell proliferation during tissue repair, and it often accompanied by the secretion of various factors, such as cytokines chemokines, known senescence-associated secretory phenotype (SASP). SASP-mediated cell-to-cell communication promotes regeneration, development. However, senescent cells can accumulate abnormally at injury sites, leading to excessive inflammation, dysfunction, intractable wounds. The effects cellular on skin wound healing be both beneficial detrimental, depending condition. Here, we reviewed functional differences in emerge healing, chronic aging. We also review latest mechanisms epidermis, dermis, subcutaneous fat, with focus senescence, regeneration. Finally, discuss potential clinical applications promoting inhibiting maximize benefits minimize detrimental effects.

Language: Английский

Citations

13
Ferroptosis and immunosenescence in colorectal cancer DOI
Yao Wang, Xinran Cao,

Chunbaixue Yang

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 106-107, P. 156 - 165

Published: Oct. 16, 2024

Language: Английский

Citations

13
Metabolic remodeling in cancer and senescence and its therapeutic implications DOI
Yeonju Kim, Yeji Jang, Mi-Sung Kim

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(8), P. 732 - 744

Published: March 6, 2024

Language: Английский

Citations

12
Senescence as a therapeutic target in cancer and age-related diseases DOI
Domhnall McHugh, Imanol Durán, Jesús Gil

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 24(1), P. 57 - 71

Published: Nov. 15, 2024

Language: Английский

Citations

10
Cellular Senescence in Hepatocellular Carcinoma: Immune Microenvironment Insights via Machine Learning and In Vitro Experiments DOI Open Access
Xinhe Lu,

Yuhang Luo,

Yun Huang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 773 - 773

Published: Jan. 17, 2025

Hepatocellular carcinoma (HCC), a leading liver tumor globally, is influenced by diverse risk factors. Cellular senescence, marked permanent cell cycle arrest, plays crucial role in cancer biology, but its markers and roles the HCC immune microenvironment remain unclear. Three machine learning methods, namely k nearest neighbor (KNN), support vector (SVM), random forest (RF), are utilized to identify eight key senescence (HCC-CSMs). Consensus clustering revealed molecular subtypes. The single-cell analysis explored microenvironment, checkpoints, immunotherapy responses. In vitro, RNA interference mediated BIRC5 knockdown, co-culture experiments assessed impact. senescence-related genes predicted survival information better than differential expression (DEGs). Eight HCC-CSMs were identified, which two distinct clusters with different clinical characteristics mutation patterns. By RNA-seq data, we investigated immunological observed that increasing cells allow hepatocytes regain population dominance. This phenomenon may be associated identified our study. combining bulk sequencing gene natural killer (NK) express at highest levels. knockdown increased NK proliferation reduced function, potentially aiding survival. These findings provide insights into senescence-driven progression potential therapeutic targets.

Language: Английский

Citations

1