Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy DOI Creative Commons
Kelly Bowlt,

Kevin S. Donnelly,

Yuting Lu

et al.

The Journal of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract Mucosal melanoma is a rare subtype associated with poor prognosis and limited existing therapeutic interventions, in part due to lack of actionable targets translational animal models for preclinical trials. Comprehensive data on this tumour type are scarce, often overlooks the importance anatomical site origin. We evaluated human canine oronasal mucosal (OMM) determine whether common disease could inform equivalent. Using primary OMM cohort treatment‐naive archival tissue, alongside clinicopathological data, we obtained transcriptomic, immunohistochemical, microbiome from both species. defined transcriptomic landscape species linked our findings microbiome, clinical data. Human dog stratified into two distinctive transcriptional groups, which using species‐independent 41‐gene signature. These subgroups termed CTLA4‐high MET‐high indicate patients. To guide decision‐making, developed immunohistochemical diagnostic tools that distinguish between subgroups. found had conserved subtypes biological similarity OMM, significant implications patient classification, treatment, trial design. © 2025 The Author(s). Journal Pathology published by John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.

Language: Английский

Defining clinically useful biomarkers of immune checkpoint inhibitors in solid tumours DOI
Ashley M. Holder, Aikaterini Dedeilia,

Kailan Sierra-Davidson

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(7), P. 498 - 512

Published: June 12, 2024

Language: Английский

Citations

74
Microbiome Dynamics: A Paradigm Shift in Combatting Infectious Diseases DOI Open Access
Mohamed Kamel,

Sami Aleya,

Majed Alsubih

et al.

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(2), P. 217 - 217

Published: Feb. 18, 2024

Infectious diseases have long posed a significant threat to global health and require constant innovation in treatment approaches. However, recent groundbreaking research has shed light on previously overlooked player the pathogenesis of disease-the human microbiome. This review article addresses intricate relationship between microbiome infectious unravels its role as crucial mediator host-pathogen interactions. We explore remarkable potential harnessing this dynamic ecosystem develop innovative strategies that could revolutionize management diseases. By exploring latest advances emerging trends, aims provide new perspective combating by targeting

Language: Английский

Citations

28
Fecal Microbiota Transplantation: Insights into Colon Carcinogenesis and Immune Regulation DOI Open Access

Olga Brusnic,

Danusia Onișor, Adrian Boicean

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(21), P. 6578 - 6578

Published: Nov. 1, 2024

Colorectal cancer (CRC) constitutes a significant global health challenge, with recent studies underscoring the pivotal role of gut microbiome in its pathogenesis and progression. Fecal microbiota transplantation (FMT) has emerged as compelling therapeutic approach, offering potential to modulate microbial composition optimize treatment outcomes. Research suggests that specific bacterial strains are closely linked CRC, influencing both clinical management interventions. Moreover, microbiome's impact on immunotherapy responsiveness heralds new avenues for personalized medicine. Despite promise FMT, safety concerns, particularly immunocompromised individuals, remain critical issue. Clinical outcomes vary widely, influenced by genetic predispositions methodologies employed. Additionally, rigorous donor selection screening protocols paramount minimize risks maximize efficacy. The current body literature advocates establishment standardized further trials substantiate FMT's CRC management. As our understanding deepens, FMT is poised become cornerstone treatment, imperative continued research validation.

Language: Английский

Citations

26
From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy DOI Creative Commons
Anqi Lin, Aimin Jiang, Lihaoyun Huang

et al.

Gut Microbes, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 18, 2025

The integration of fecal microbiota transplantation (FMT) with immune checkpoint inhibitors (ICIs) presents a promising approach for enhancing cancer treatment efficacy and overcoming therapeutic resistance. This review critically examines the controversial effects FMT on ICIs outcomes elucidates underlying mechanisms. We investigate how modulates gut composition, microbial metabolite profiles, tumor microenvironment, thereby influencing effectiveness. Key factors efficacy, including donor selection criteria, recipient characteristics, administration protocols, are comprehensively discussed. delineates strategies optimizing formulations systematically monitoring post-transplant microbiome dynamics. Through comprehensive synthesis evidence from clinical trials preclinical studies, we elucidate potential benefits challenges combining across diverse types. While some studies report improved outcomes, others indicate no benefit or adverse effects, emphasizing complexity host-microbiome interactions in immunotherapy. outline critical research directions, encompassing need large-scale, multi-center randomized controlled trials, in-depth ecology multi-omics approaches artificial intelligence. Regulatory ethical addressed, underscoring imperative standardized protocols rigorous long-term safety assessments. seeks to guide future endeavors applications FMT-ICIs combination therapy, improve patient while ensuring both efficacy. As this rapidly evolving field advances, maintaining judicious balance between openness innovation cautious scrutiny is crucial realizing full modulation

Language: Английский

Citations

12
Microbiome Integrity Enhances the Efficacy and Safety of Anticancer Drug DOI Creative Commons
Alice Njolke Mafe, Dietrich Büsselberg

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 422 - 422

Published: Feb. 10, 2025

The intricate relationship between anticancer drugs and the gut microbiome influences cancer treatment outcomes. This review paper focuses on role of integrity in enhancing efficacy safety drug therapy, emphasizing pharmacokinetic interactions microbiota. It explores how disruptions to composition, or dysbiosis, can alter metabolism, immune responses, side effects. By examining mechanisms disruption caused by drugs, this highlights specific case studies like cyclophosphamide, 5-fluorouracil, irinotecan, their impact microbial diversity clinical also discusses microbiome-targeted strategies, including prebiotics, probiotics, postbiotics, fecal microbiota transplantation (FMT), as promising interventions enhance treatment. Furthermore, potential profiling personalizing therapy integrating these into practice is explored. Finally, proposes future research directions, developing novel biomarkers a deeper comprehension drug-microbiome interactions, respond current gaps knowledge improve patient outcomes care.

Language: Английский

Citations

6
Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma DOI Creative Commons

Chengpei Zhu,

Chenchen Zhang, Shanshan Wang

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(6), P. e008686 - e008686

Published: June 1, 2024

Background The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom microbiome alterations interactions ICI-treated HCC cohorts are not fully understood. Methods From November 2018 April 2022, patients receiving ICI treatment for advanced were prospectively enrolled. Herein, we investigated microbiota characterization of microbiome, mycobiome, metabolome using metagenomic, ITS2, metabolomic data sets 80 with HCC. Results Our findings demonstrated that metabolites differed significantly durable clinical benefit (DCB) non-durable (NDB) groups, whereas differences smaller fungi. overall diversity fungi before was higher DCB group than NDB group, difference began change use immunotherapy after 6–8 weeks. We also explored microbes established 18 bacterial species models as predictive biomarkers predicting whether is sustained (area under curve=75.63%), screened two ( Actinomyces_sp_ICM47 , Senegalimassilia_anaerobia ) one metabolite (galanthaminone) prognostic survival treated ICI. Conclusions In this study, status microbiota, including bacteria, fungi, their metabolites, described by multiomics sequencing first time demonstrate potential taxa efficacy, biomarkers.

Language: Английский

Citations

10
Gut microbiota interact with breast cancer therapeutics to modulate efficacy DOI Creative Commons
Alana A. Arnone,

Katherine Ansley,

Arielle L. Heeke

et al.

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Abstract The gut microbiome, or the community of microorganisms residing in gastrointestinal tract, has emerged as an important factor breast cancer etiology and treatment. Specifically, impact bacterial populations on therapeutic outcomes is emerging area research. microbiota’s role modifying pharmacokinetics chemotherapy endocrine-targeting therapies can alter drug efficacy toxicity profiles. In addition, microbiome’s capacity to regulate systemic inflammation immune responses may influence effectiveness both conventional immunotherapeutic strategies for treatment cancer. Overall, while bidirectional interactions between microbiome are still being studied, its increasingly recognized. Future research provide more definitive insights help develop personalized harness improve outcomes.

Language: Английский

Citations

2
Gut Microbiota–Tumor Microenvironment Interactions: Mechanisms and Clinical Implications for Immune Checkpoint Inhibitor Efficacy in Cancer DOI Creative Commons

Sawsan Sudqi Said,

Wisam Nabeel Ibrahim

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 171 - 192

Published: Jan. 1, 2025

Cancer immunotherapy has transformed cancer treatment in recent years, with immune checkpoint inhibitors (ICIs) emerging as a key therapeutic approach. ICIs work by inhibiting the mechanisms that allow tumors to evade detection. Although have shown promising results, especially solid tumors, patient responses vary widely due multiple intrinsic and extrinsic factors within tumor microenvironment. Emerging evidence suggests gut microbiota plays pivotal role modulating at site may even influence outcomes patients receiving ICIs. This review explores complex interactions between microenvironment, examining how these could impact effectiveness of ICI therapy. Furthermore, we discuss dysbiosis, an imbalance composition, contribute resistance ICIs, highlight microbiota-targeted strategies potentially overcome this challenge. Additionally, studies investigating diagnostic potential profiles patients, considering microbial markers might aid early detection stratification By integrating insights from preclinical clinical studies, aim shed light on microbiome modulation adjunct tool, paving way for personalized approaches optimize outcomes.

Language: Английский

Citations

2
Deciphering Host–Virus Interactions and Advancing Therapeutics for Chronic Viral Infection DOI Creative Commons
Majid Eslami,

Neda Arjmand,

Fatemeh Mahmoudian

et al.

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 390 - 390

Published: March 10, 2025

Chronic viral infections like HIV, HBV, and HCV establish persistent interactions with the host immune system, resulting in evasion long-term dysfunction. These viruses use a range of strategies to limit defenses, such as downregulating MHC class I, disrupting interferon signaling, altering apoptosis pathways, suppressing cytotoxic T-cell activity. Key proteins, including HIV Nef, HBV X protein, NS5A, interfere antigen presentation JAK/STAT thereby reducing antiviral responses. induce exhaustion due exposure, which leads expression inhibitory receptors PD-1 CTLA-4 on T cells. Viral epigenetic changes, N6-methyladenosine modifications histone deacetylation, enhance by modulating gene infected Viruses further manipulate cytokine networks promoting an immunosuppressive environment through IL-10 TGF-β secretion, suppress inflammatory responses inhibit activation. This review examines molecular/cellular mechanisms that enable chronic escape immunity, focusing antigenic variation, disruption, control apoptotic pathways. It also addresses how genetic factors, HLA polymorphisms, influence disease progression. Lastly, we discuss host-targeted therapies, checkpoint inhibitors, treatments, CRISPR.

Language: Английский

Citations

2
FLT3 -mutated AML: Immune Evasion Through Exosome-Mediated Mechanisms and innovative combination therapies targeting Immune escape DOI

Mohamed J. Saadh,

Waleed K. Abdulsahib,

Dilfuza Ashurova

et al.

Expert Review of Anticancer Therapy, Journal Year: 2025, Volume and Issue: 25(2), P. 143 - 150

Published: Jan. 31, 2025

Acute Myeloid Leukemia is a heterogeneous hematological malignancy characterized by the uncontrolled proliferation of abnormal myeloid cells. Besides several other genetic abnormalities developed in AML, FLT3 mutations are significant due to their worse prognostic impacts and therapeutic resistance. As result, these enable AML cells develop mechanisms for evading immune surveillance. This review discusses ways escape FLT3-mutated A literature search was conducted on PubMed, Scopus, Web Science databases, covering articles published between 2010 2024 with related keywords. The discussion covers cells' downregulation recognition markers, expression checkpoint proteins, establishment an immunosuppressive tumor microenvironment. Specific attention given small extracellular vesicles participation escape. focus exosome-mediated pathways possible combination therapies. represent formidable challenge crucial role evasion. Exosomes major players processes. Combination therapies targeting exosome pathway could significantly improve patients' overall outcomes. Understanding underlying mechanisms, including targeted therapies, will be required transcend existing limitations push newer strategies treatment.

Language: Английский

Citations

1