Regulatory T cell-associated gene signature correlates with prognostic risk and immune infiltration in patients with breast cancer DOI Open Access
Jie Wu,

Gaiping Zhao,

Yan Cai

et al.

Translational Cancer Research, Journal Year: 2024, Volume and Issue: 13(12), P. 6766 - 6781

Published: Dec. 1, 2024

Regulatory T cells (Tregs) play a pivotal role in the development, prognosis, and treatment of breast cancer. This study aimed to develop Treg-associated gene signature that contributes predict prognosis therapy benefits genes were screened based on single-cell RNA-sequencing (RNA-seq) TISCH2 database bulk RNA-seq The Cancer Genome Atlas (TCGA) database. was identified via survival analysis, univariate cox, least absolute shrinkage selection operator (LASSO) multivariable Cox regression analyses. Immune status assessed using single-sample set enrichment analysis (ssGSEA) Estimation STromal MAlignant Tumor tissues Expression data (ESTIMATE) algorithms. Drug sensitivity estimated pRRophetic. Gene (GSEA) conducted explore changed pathways. A total 169 as genes, close interactions existed among these genes. Kaplan-Meier (KM) cox revealed 29 prognostic (all P<0.05), finally six-gene including TBC1D4, PMAIP1, IFNG, LEF1, MZB1 EZR by LASSO Cox. Based this signature, patients high-risk group exhibited worse probability than those low-risk TCGA training dataset (P<0.001). Additionally, showed moderate predictive power for 1-, 3- 5-year cancer both [area under curve (AUC) =0.705, 0.678 0.668, respectively]. Similar also observed validation datasets. Risk scores significantly differed between subgroups divided clinicopathologic features, especially molecular subtypes. Patients high- groups significant differences infiltration abundance multiple types immune (such as, activated B cells/CD8+ cells/CD4+ cells), stromal P<0.05). Moreover, 83 chemotherapeutic drugs such lapatinib, methotrexate, gefitinib two risk P<0.001). is first cancer, which could help identify who might be benefit from immunotherapy and/or chemotherapy.

Language: Английский

The diagnostic value of a breast cancer diagnosis model based on serum MiRNAs and serum tumor markers DOI Creative Commons
Xiaohui Li, Feng Wang, Faquan Lin

et al.

World Journal of Surgical Oncology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 29, 2025

Abstract Background Breast cancer (BCa) is the leading cause of cancer-related death among women worldwide. MicroRNAs (miRNAs) are promising tools for diagnosis and prognosis. This study investigated role serum miRNAs tumor markers (TMs) in BCa. Methods Differentially expressed were screened from samples BCa patients healthy individuals via high-throughput sequencing. The expression hsa-miR-1911-3p, hsa-miR-4694-5p, hsa-miR-548ao-5p, hsa-miR-4804-3p 169 116 controls was detected qRT-PCR. Serum tumor-associated antigens by chemiluminescence. Logistic regression subsequently used to develop miRNA panel I, TM II, (miRNA + TM) III models. Receiver operating characteristic (ROC) curve, precision-recall (PR) curve decision analyses (DCA) performed assess accuracy three models diagnosis. Additionally, relationships between clinical characteristics with assessed. Results Four (hsa-miR-1911-3p, hsa-miR-4804-3p) newly associated I based on hsa-miR-548ao-5p showed greater diagnostic effectiveness than II antigen 125 (CA125) 153 (CA153), AUC values 0.816 0.777, respectively. had higher an value 0.870. miR-548ao-5p miR-4804-3p closely related features, such as human epidermal growth factor receptor 2 (HER2), estrogen (ER), progesterone (PR), HER2-enriched subtype, stage III/IV, lymph node-transplanted breast cancer. Conclusion MiR-548ao-5p miR-4804-3 could serve potential biomarkers

Language: Английский

Citations

0

Poloxamer-based drug delivery systems: Frontiers for treatment of solid tumors DOI Creative Commons

Mehdi Pourbakhsh,

Masoud Jabraili,

Morteza Akbari

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101727 - 101727

Published: April 1, 2025

Pluronics or poloxamers are a type of triblock copolymer. These non-ionic molecules consist hydrophobic block embedded in two hydrophilic parts. have become favorite materials for use the field biomedical research due to having favorable physicochemical and biological properties such as amphiphilicity, solubility ionic solutions, biocompatibility, biodegradability, self-assembly low toxicity. The scope these applications can vary from tissue engineering drug delivery. One important uses pluronics is deliver drugs various cancer cells. Herein we first provide an overview on variety ploronic biomaterials. And then intensively evaluate their potential delivery systems (DDSs) treatment solid tumors with special focus breast cancers. After explaining pros cons pluronics, current status clinical settings future prospects highlighted.

Language: Английский

Citations

0

Comprehensive Analysis of Oncogenic Somatic Alterations of Mismatch Repair Gene in Breast Cancer Patients DOI Creative Commons
Yan Yin, Yang Wang,

Jin-Hai Tang

et al.

Bioengineering, Journal Year: 2025, Volume and Issue: 12(4), P. 426 - 426

Published: April 18, 2025

Recent clinical trials have suggested that solid cancers with mismatch repair (MMR) deficiency are highly responsive to immunotherapy, regardless of cancer types. Previous MMR-related studies on breast predominantly focused germline variants. However, the somatic MMR alterations not been comprehensively characterized in cancer. In this study, we integrated genomic, transcriptomic, and data from over 3000 cases across six public cohorts. Our findings revealed 1.2% harbored oncogenic alterations, triple-negative (TNBC) demonstrating highest mutation rate at 3.1%. Additionally, were significantly associated microsatellite instability-high (MSI-H) mutational signatures, indicating led impaired function system. Biallelic inactivation genes resulted a more pronounced loss compared monoallelic inactivation. Importantly, these increased tumor burden (TMB) neoantigen load cancer, MSI-H status. These indicate frequency is TNBC can lead functional deficiencies, suggesting some patients harboring such may benefit immunotherapy.

Language: Английский

Citations

0

Intratumoral Immunotherapy in Breast Cancer DOI Creative Commons
Camille C. Baumrucker, Nicole C. Harris,

Susan Hoover

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 429 - 429

Published: April 19, 2025

Breast cancer remains the most frequently diagnosed and second highest cause of death in females. Metastatic recurrence that is resistant to traditional therapies presents a major challenge, necessitating development an innovative treatment strategy. Immunotherapy has gained popularity cancer, particularly melanoma, lung more recently breast cancer. Major developments immunotherapy have been made with better understanding tumor microenvironment how can be manipulated induce anti-tumor immune response. Intratumorally delivered used create local This review provides comprehensive overview intratumoral for its resultant changes microenvironment. The discussed immunotherapeutics include oncolytic viruses, nucleic acids, innate agonists, bacteria, chimeric antigen receptor T cells, dendritic cells. also evaluates completed clinical trials using these therapies. Lastly, offers future perspectives immunotherapy.

Language: Английский

Citations

0

Photodynamic Biomimetic Liposomes Targeted to the Endoplasmic Reticulum Enhance Combined Immunotherapy for Triple-Negative Breast Cancer DOI
Tianyang Li,

Haimei Meng,

Xinfeng Huang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Cancer immunotherapies, such as immune checkpoint inhibitors, have advanced rapidly and achieved notable success, yet they face significant challenges due to poor response rates immune-related adverse effects, particularly in cases of triple-negative breast cancer (TNBC). Photodynamic therapy (PDT) can initiate immunogenic cell death (ICD) by inducing endoplasmic reticulum (ER) stress, thereby enhancing the effectiveness tumor immunotherapy. Herein, we develop potent PDT biomimetic liposomes (PB Lipo) locating ER realize a synergistic immuno-photodynamic treatment. The PB Lipo is prepared using optimal ratios phospholipids membrane. It then loaded with indocyanine green (ICG), photosensitizer approved for clinical use. has unique ability accumulate via membrane fusion, leading severe stress when exposed near-infrared (NIR) laser light, thus intensifying ICD. In combination antiprogrammed death-ligand 1 (PD-L1) antibody (αPD-L1), significantly improves efficiency against tumors xenograft TNBC models. As result, our combined treatment enhances mature dendritic cells, activates CD4+ T CD8+ promotes secretion cytotoxic cytokines. Collectively, findings reveal that Lipo-mediated presents viable approach effectively targeting ICD, boosting antitumor efficacy TNBC.

Language: Английский

Citations

0

Immunotherapy-Based Combination Therapy for the Successful Treatment of Coexisting Primary and Axillary Accessory Breast Cancers: A Case Report DOI Open Access
Yuko Tanaka, Yoshio Suzuki

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Language: Английский

Citations

0

Tumor-associated MerTK promotes a pro-inflammatory microenvironment and enhances immune checkpoint inhibitor response in triple-negative breast cancer DOI Creative Commons
Bridget E. Crossman,

Regan L. Harmon,

Mari Iida

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: May 5, 2025

Introduction Triple-negative breast cancer (TNBC) is an aggressive subtype of with no targeted treatment modalities. Currently, combination chemotherapy and immune checkpoint inhibitor (ICI) therapy are options for many TNBC patients; however, their efficacy limited. Understanding what makes TNBCs responsive to crucial improving patient outcomes. Methods We investigated the role MerTK expression in using syngeneic immunodeficient mouse models, human murine cells lines, clinical samples. Flow cytometry, immunohistochemistry, RNA, multiplex ELISA, immunohistochemistry immunofluorescence analysis were used probe effects on tumor microenvironment. Results Overexpression models leads a marked delay growth, coupled significant increases anti-tumor M1 macrophage, CD4+ T cell, active CD8+ NK NKT cell populations. This increase pro-inflammatory contrasted decreased anti-inflammatory polymorphonuclear myeloid-derived suppressor (PMN-MDSCs) regulatory (Tregs) TIME. In addition, tumors overexpressing exhibited very high sensitivity both aPDL1 aCTLA4 therapies, leading durable control and, some cases, complete regression without recurrence. Further, Vectra multispectral analysis, elevated samples was associated increased levels cells. vivo data suggest that tumor-bound independent PD-L1 TNBC. Conclusion These preclinical findings indicate could serve as predictive biomarker ICI response TNBC, potentially expanding cohort late-stage patients eligible while reducing toxicity early-stage by treating only those predicted respond.

Language: Английский

Citations

0

Neutrophil-Camouflaged Stealth Liposomes for Photothermal-Induced Tumor Immunotherapy Through Intratumoral Bacterial Activation DOI Creative Commons

Xinxin Chen,

Jiang Sun,

Tingxian Ye

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(5), P. 614 - 614

Published: May 5, 2025

Objective: F. nucleatum, a tumor-resident bacterium colonizing breast cancer (BC), results in an immunosuppressive microenvironment and facilitates tumor growth metastasis. This study aimed to develop neutrophil-based liposome delivery system designed for dual-targeted elimination of cells while simultaneously upregulating pathogen-associated molecular patterns damage-associated potentiate immunotherapy. Methods: The liposomes (PD/GA-LPs) loaded with the perylene diimide complex (PD) gambogic acid (GA) were fabricated via extrusion method. Subsequently, comprehensive evaluations including physicochemical characteristics, antibacterial activity, antitumor effect, immunomodulatory effect evaluation systematically conducted validate feasibility this system. Results: resulting PD/GA-LPs exhibited dynamic size (121.3 nm, zeta potential −44.1 mV) high encapsulation efficiency approximately 78.1% 91.8% (GA). In addition, optimized excellent photothermal performance efficacy. vitro cellular experiments revealed that enhanced internalization by neutrophils, followed extracellular trap-mediated release, ultimately significantly inhibiting cell proliferation inducing immunogenic death. During vivo treatment, targeted accumulation, where nucleatum-driven PD reduction activated near-infrared-responsive ablation. When combined GA, effectively eliminated facilitating subsequent T-cell infiltration. Conclusions: strategy amplified immune response, thus leading effective treatment BC prevention summary, approach, grounded distinct microecology normal tissues, offers novel insights into development precise potent immunotherapies BC.

Language: Английский

Citations

0

The Genomic and Biologic Landscapes of Breast Cancer and Racial Differences DOI Open Access

Sampath Rukshani Galappaththi,

Kelly R. Smith,

Enas S. Alsatari

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13165 - 13165

Published: Dec. 7, 2024

Breast cancer is a significant health challenge worldwide and the most frequently diagnosed among women globally. This review provides comprehensive overview of breast biology, genomics, microbial dysbiosis, focusing on its various subtypes racial differences. primarily classified into carcinomas sarcomas, with constituting cases. Epidemiology risk factors are important for public intervention. Staging grading, based TNM Nottingham grading systems, respectively, crucial to determining clinical outcome treatment decisions. Histopathological include in situ invasive carcinomas, such as ductal carcinoma (IDC) lobular (ILC). The explores molecular subtypes, including Luminal A, B, Basal-like (Triple Negative), HER2-enriched, delves cancer's histological progression patterns. Recent research findings related nuclear mitochondrial genetic alterations, epigenetic reprogramming, role microbiome dysbiosis differences also reported. an update current diagnostics modalities.

Language: Английский

Citations

3

Comprehensive Transcriptome Analysis Expands lncRNA Functional Profiles in Breast Cancer DOI Open Access
Wenyong Zhu, Hao Huang,

Zixi Hu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8456 - 8456

Published: Aug. 2, 2024

Breast cancer is a heterogeneous disease that arises as multi-stage process involving multiple cell types. Patients diagnosed with the same clinical stage and pathological classification may have different prognoses therapeutic responses due to alterations in molecular genetics. As an essential marker for subtyping of breast cancer, long non-coding RNAs (lncRNAs) play crucial role gene expression regulation, differentiation, maintenance genomic stability. Here, we developed modular framework lncRNA identification applied it cohort identify novel lncRNAs not previously annotated. To investigate potential biological function, regulatory mechanisms, relevance lncRNAs, elucidated chromatin features these along associated protein-coding genes putative enhancers involved networks. Furthermore, uncovered patterns annotated identified were related hormone response PAM50 criterion, well immune progression states across cells checkpoint genes. Collectively, comprehensive functional analysis revealed by altering participating networks, contributing better insight into heterogeneity avenues intervention.

Language: Английский

Citations

1