Dynamic evolution and antitumor mechanisms of CXCR6+CD8+ T cells in small cell lung cancer treated with low-dose radiotherapy and immunotherapy DOI Creative Commons

Lin Guo,

Zhuoran Yao, Kai Kang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 17, 2025

Patients with small-cell lung cancer (SCLC) have the poor prognosis. Current research suggested that low-dose radiotherapy (LDRT) combined immunotherapy can enhance immunogenicity of tumor cells, thereby improving antigen presentation and promoting intratumoral infiltration CD8+ T which significantly extends survival patients. However, change trajectory mechanisms underlying promotion enhancement their cytotoxic functions remain to be elucidated. To delineate dynamic changes we collected tumors from Kaede tumor-bearing mice had undergone radioimmunotherapy. Using flow cytometry, sorted intratumoral-infiltrating immune were required for single-cell RNA sequencing, at various time points (Kaede Red: derived tumor-draining lymph node [TDLN]). The results obtained sequencing analysis further validated through experiments, such as immunofluorescence, clinical cohort data. Here, observed stem-like cells migrating TDLN site differentiating into effector phenotypes within tumor. Dendritic (DCs) are key cluster induces differentiation cell phenotypes. Moreover, SCLC patients a high tumor-specific CXCR6+CD8+ exhibited supportive TME longer (P < 0.001). This study delineates identifies crucial role DCs in differentiation, highlights significance anti-tumor immunity. Future therapeutic strategies could focus on enhancing activated microenvironment improve treatment efficacy.

Language: Английский

The need to establish and recognize the field of clinical laboratory science (CLS) as an essential field in advancing clinical goals DOI Creative Commons
Mojtaba Aghaei, Reyhane Khademi, Seyed Sobhan Bahreiny

et al.

Health Science Reports, Journal Year: 2024, Volume and Issue: 7(8)

Published: Aug. 1, 2024

Language: Английский

Citations

42

Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets DOI Creative Commons
Atieh Raoufi, Hamed Soleimani Samarkhazan, S Nouri

et al.

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 6, 2025

Graft-versus-host disease remains one of the most formidable barriers to complete success hematopoietic stem cell transplantation that has emerged as curative approach for many malignancies because it affects quality life and overall survival. Macrophages are among important members immune system, which perform dual roles in GVHD both therapeutic tools targets. This review epitomizes multifunctional role macrophages pathophysiology acute chronic GVHD. play an early phase their recruitment infiltration into target organs. Furthermore, they polarize two functionally different phenotypes, including M1 M2. In case GVHD, express phenotype characterized by production pro-inflammatory cytokines contribute tissue damage. contrast, tend toward M2 associated with repair tissues fibrosis. A critical balance these phenotypes is central course severity Further interactions other lymphocytes such T cells, B fibroblast further determine Macrophage interaction alloreactive cells promotes inflammation. therefore inducing injuries during Interaction macrophages, cell, fibroblast, CD4+ fibrosis and, hence, subsequent dysfunction These some insights, while several challenges remain. First, impact dominant on polarization incompletely sometimes controversial. Second, development targeted therapies able modulate macrophage function without systemic side effects area ongoing investigation. Future directions involve exploration macrophage-targeted therapies, small molecules, antibodies, nanotechnology, behavior improve patient outcomes. underlines fact a profound understanding essential developing new more effective strategies. Targeting might represent avenue decreasing incidence improving safety HSCT.

Language: Английский

Citations

9

New insights on anti-tumor immunity of CD8+ T cells: cancer stem cells, tumor immune microenvironment and immunotherapy DOI Creative Commons

Yibin Lin,

Yifu Song, Yaochuan Zhang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 17, 2025

Abstract Recent breakthroughs in tumor immunotherapy have confirmed the capacity of immune system to fight several cancers. The effective means treating cancer involves accelerating death cells and improving patient immunity. Dynamic changes microenvironment alter actual effects anti-tumor drug production may trigger favorable or unfavorable responses by modulating tumor-infiltrating lymphocytes. Notably, CD8 + T are one primary that provide response. Tumor stem will resist evade destruction through various mechanisms as exert their function. This paper reviews research on regulation development prognosis directly indirectly role cells. We also discuss related strategies.

Language: Английский

Citations

4

Increased nerve density adversely affects outcome in colorectal cancer and denervation suppresses tumor growth DOI Creative Commons
Hao Wang,

Ruixue Huo,

Kexin He

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 23, 2025

The colon and rectum are highly innervated, with neural components within the tumor microenvironment playing a significant role in colorectal cancer (CRC) progression. While perineural invasion (PNI) is associated poor prognosis CRC, impact of nerve density diameter on behavior remains unclear. This study aims to evaluate prognostic value characteristics CRC verify nerves growth. Tissue samples from 129 patients were stained immunofluorescent markers NF-L S100B detect nerves. Nerve measured normalized. Kaplan-Meier survival analysis Cox regression models used identify factors. Prognostic established using receiver operating characteristic (ROC) curve assess predictive A murine chemical denervation model was employed disrupt sympathetic 6-hydroxydopamine, inhibit muscarinic receptor 3 darifenacin, ablate sensory neurons capsaicin. total 0.72 ± 0.59/mm², intratumoral (0.42 0.40/mm²) being significantly lower than extratumoral regions (1.00 0.75/mm²). average 28.14 6.04 μm, no difference between (28.2 7.65 μm) (27.86 6.72 μm). PNI observed 65 (50.4%). high normalized (NND) shorter overall disease-free patients, identified as an independent factor. Patients exhibit higher NND. Incorporating NND into ROC improved sensitivity specificity predictions. In model, sympathetic, parasympathetic, reduced rectal volume. critical factors influencing patient enhance accuracy prediction models. Moreover, effectively inhibits growth vivo, highlighting potential targeting therapeutic strategy CRC.

Language: Английский

Citations

2

Algorithms and tools for data-driven omics integration to achieve multilayer biological insights: a narrative review DOI Creative Commons
Aurelia Morabito, Giulia De Simone, Roberta Pastorelli

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 10, 2025

Systems biology is a holistic approach to biological sciences that combines experimental and computational strategies, aimed at integrating information from different scales of processes unravel pathophysiological mechanisms behaviours. In this scenario, high-throughput technologies have been playing major role in providing huge amounts omics data, whose integration would offer unprecedented possibilities gaining insights on diseases identifying potential biomarkers. the present review, we focus strategies applied literature integrate genomics, transcriptomics, proteomics, metabolomics year range 2018-2024. Integration approaches were divided into three main categories: statistical-based approaches, multivariate methods, machine learning/artificial intelligence techniques. Among them, statistical (mainly based correlation) ones with slightly higher prevalence, followed by learning Integrating multiple layers has shown great uncovering molecular mechanisms, putative biomarkers, aid classification, most time resulting better performances when compared single analyses. However, significant challenges remain. The nature platforms introduces issues such as variable data quality, missing values, collinearity, dimensionality. These further increase combining datasets, complexity heterogeneity integration. We report found cope these challenges, but some open still remain should be addressed disclose full

Language: Английский

Citations

2

Neuroinflammation and energy metabolism: a dual perspective on ischemic stroke DOI Creative Commons
Lei Wen, Hao Zhuang, Weiyi Huang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 10, 2025

Ischemic stroke is a prevalent form of cerebrovascular accident, with its pathogenesis involving the intricate interplay between neuroinflammation and energy metabolism. Cerebral ischemia disrupts oxygen supply, triggering metabolic dysregulation activating neuroinflammatory responses, ultimately resulting in cellular damage. This review provides an exhaustive analysis complex mechanisms ischemic stroke, particular focus on interaction The interruption supply due to cerebral initiates activates including release inflammatory cytokines activation immune cells, contributing damage further disturbances. Studies indicate that metabolism significantly impairs neural cell function interacts neuroinflammation, exacerbating brain injury. Therapeutic strategies primarily concentrate modulating suppressing emphasizing importance in-depth research into their provide theoretical foundation for new treatment stroke. Future should how balance anti-inflammatory regulation minimize promote recovery.

Language: Английский

Citations

1

Identifying disease progression biomarkers in metabolic associated steatotic liver disease (MASLD) through weighted gene co-expression network analysis and machine learning DOI Creative Commons
Weiliang Zhang,

Weirong Lu,

Yaqi Jiao

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 24, 2025

Metabolic Associated Steatotic Liver Disease (MASLD), encompassing conditions simple liver steatosis (MAFL) and metabolic associated steatohepatitis (MASH), is the most prevalent chronic disease. Currently, management of MASLD impeded by lack reliable diagnostic biomarkers effective therapeutic strategies. We analyzed eight independent clinical datasets from GEO database. Differential expression weighted gene co-expression network analyses (WGCNA) were used to identify 23 genes related inflammation. Five hub selected using machine learning techniques (SVM-RFE, LASSO, RandomForest) combined with a literature review. Nomograms created predict incidence, potential was evaluated through receiver operating characteristic (ROC) curves. Additionally, Protein-Protein Interaction (PPI) networks, functional enrichment, immune infiltration performed. Potential transcription factors agents also explored. Finally, biological significance these validated animal model, histological examination transcriptomic profiles. identified five genes-UBD/FAT10, STMN2, LYZ, DUSP8, GPR88-that are for MASLD. These exhibited strong potential, either individually or in combination. This study highlights key as promising candidates understanding findings offer new insights into disease's pathophysiology may contribute development better approaches.

Language: Английский

Citations

1

PRMT6 promotes colorectal cancer progress via activating MYC signaling DOI Creative Commons
Xin Zhang,

Mingxin Jin,

Yali Chu

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 16, 2025

Colorectal cancer (CRC) remains a major global health challenge, with high rates of incidence and mortality. This study investigates the role protein arginine methyltransferase 6 (PRMT6) as an oncogene in CRC its mechanistic involvement tumor progression. We found that PRMT6 is significantly overexpressed tissues compared to adjacent normal associated poorer patient survival. Functional assays demonstrated promotes cell proliferation, migration, invasion. Mechanistically, enhances MYC signaling by stabilizing c-MYC through mono-methylation at 371, which inhibits poly-ubiquitination subsequent degradation. post-translational modification crucial for PRMT6-induced proliferation. Xenograft models further validated knockdown results reduced growth decreased levels. Our findings highlight key regulator stability progression, suggesting targeting or effects on could offer promising strategy treatment.

Language: Английский

Citations

0

Application of nanoparticles with activating STING pathway function in tumor synergistic therapy DOI
Yi Yang,

Yaning Fang,

Xin‐Yu Du

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114013 - 114013

Published: Jan. 18, 2025

Language: Английский

Citations

0

PTOV1 exerts pro-oncogenic role in colorectal cancer by modulating SQSTM1-mediated autophagic degradation of p53 DOI Creative Commons

Yongli Fan,

Yuqin Li,

Xia Luo

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 4, 2025

Prostate Tumor Overexpressed 1 (PTOV1) is overexpressed and associated with malignant phenotypes in various types of tumors. However, the detailed roles PTOV1 its underlying mechanism CRC remain unclear. The clinical significance was assessed databases samples. effects on tumor-associated were detected by several vitro assays vivo mouse models. Immunoprecipitation (IP) combined protein mass spectrometry Co-Immunoprecipitation (Co-IP) used to identify p53 interacting PTOV1. Immunofluorescence assay, western blot transmission electron microscopy (TEM) analysis evaluated autophagy. Here, we revealed that highly expressed human tissues, especially at advanced stages, reduced survival time among patients. upregulated promoted cell proliferation, migration, invasion, tumor growth metastasis cells vivo. At molecular level, destabilized activating autophagy recruiting for cargo receptor SQSTM1 directed autophagic degradation. There a negative expression correlation between tissues. Moreover, overexpression or knockdown reversed pro-tumor CRC. Our study unveils oncogenic role progression, which achieved promoting degradation p53. These findings highlight potential targeting PTOV1-SQSTM1-p53 axis as therapeutic approach

Language: Английский

Citations

0