A newly constructed STC2/FPR1 dual genes signature works as a prognosis risk indicator with implication in the macrophages dominated and TIM-3 checkpoint related osteosarcoma immune landscape DOI Creative Commons
Wenxia Ma, Lei Miao, Siying Liu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Abstract Background Osteosarcoma has been a common bone malignancy occurring in children and adolescents. Attributing to high tumor heterogeneity, none specific breakthrough received targeted gene therapy for osteosarcoma, although it’s still of great potential immunotherapy clinical application. In the study, 5 GEO profiles containing transcriptome information 109 osteosarcoma samples, single cell sequencing data composed 6 cases as well 43 local hospital tissue samples were combine used identify promising immune related candidate genes osteosarcoma. Methods Based on microarrays from database profile IMMPORT database, differently expressed meanwhile candidates comparing normal control identified. Then, protein-protein interaction network (PPI), survival analysis followed by LASSO succession applied construct signature based selected genes. After understanding basic genetic physicochemical properties evaluating prognosis risk association using cancer its with microenvironment features including macrophages included various cells infiltration, different checkpoints expression, signaling pathways involvement next step assessed. Results From datasets which contains total 108 level PPI highlighted cluster Further, ROC curve Cox regression assisted scaled hub down 2 key genes, namely STC2 FPR1, was constructed them. double staining immunochemistry (IHC) experiment date revealed that mainly cells, meanwhile, FPR1 mostly enriched focused also main type microenvironment. Moreover, combining STC2/FPR1 dual associated distribution multiple checkpoints, especially TIM-3. correlation between other death (ICD) ESTIMATE score additionally evaluated. Conclusions analysis, constructed. Immune indicated infiltration ans it TIM-3 expression. The results shall benefit further researches assist revealing prediction markers immunotherapy.

Язык: Английский

The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies DOI Creative Commons
Xiaowen Han,

Jiayi Zhang,

Weidong Li

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 21, 2025

Immunotherapy has emerged as a preeminent force in the domain of cancer therapeutics and achieved remarkable breakthroughs. Nevertheless, high resistance become most substantial impediment restricting its clinical efficacy. Beta-2 microglobulin (B2M), light chain major histocompatibility complex (MHC) class I, plays an indispensable part by presenting tumor antigens to cytotoxic T lymphocytes (CTLs) for exerting anti-tumor effects. Accumulating evidence indicates that B2M mutation/defect is one key mechanisms underlying immunotherapy resistance. Therefore, elucidating role played devising effective strategies battle against are pressing issues. This review will systematically expound upon them, aiming provide insight into potential promising target anticancer immune response.

Язык: Английский

Процитировано

2
Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies DOI Open Access
Nicolas Roussot,

Courèche Kaderbhaï,

François Ghiringhelli

и другие.

Cancers, Год журнала: 2025, Номер 17(5), С. 906 - 906

Опубликована: Март 6, 2025

Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immunotherapy targeting the PD-1/PD-L1 axis has revolutionized treatment, providing durable responses in subset patients. However, with fewer than 50% patients achieving significant benefits, there is critical need to expand therapeutic strategies. This review explores emerging targets immune checkpoint inhibition beyond PD-1/PD-L1, including CTLA-4, TIGIT, LAG-3, TIM-3, NKG2A, and CD39/CD73. We highlight biological basis CD8 T cell exhaustion shaping antitumor response. Novel approaches additional inhibitory receptors (IR) are discussed, focus on their distinct mechanisms action combinatory potential existing therapies. Despite advancements, challenges remain overcoming resistance optimizing patient selection. underscores importance dual blockade innovative bispecific antibody engineering maximize outcomes for NSCLC

Язык: Английский

Процитировано

1
Development of a prognostic model based on four genes related to exhausted CD8+ T cell in triple-negative breast cancer patients: a comprehensive analysis integrating scRNA-seq and bulk RNA-seq DOI Creative Commons
Yulin Shi, Yang Yu, J. Zhao

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 3, 2025

Low immune infiltration is closely associated with poor clinical results and an unfavorable response to therapy in triple-negative breast cancer (TNBC). T-cell exhaustion (TEX) a significant risk factor for tumor immunosuppression invasion. Although improving TEX enhancing effector function are promising strategies strengthening immunotherapy, their role the pathogenesis of TNBC remains unclear. This study's objective was develop prognostic model based on exhausted CD8+ (CD8+ Tex)-related differentially expressed genes (DEGs) investigate its relevance. Initially, 398 Tex-related were screened utilizing single-cell RNA sequencing (scRNA-seq) data from patients. Pseudotime analysis confirmed that Tex mainly clustered at end differentiation pathways, making them critical subset progression. By analyzing TCGA cohort, ten DEGs identified as significantly correlated overall survival (OS) patients, containing four biomarkers (GBP1, CTSD, ABHD14B, HLA-A) constructed. The demonstrated robust predictive capability both cohort external low-risk group exhibiting elevated expression immunological checkpoint molecules cell infiltration, well better responses immunotherapy chemotherapy. Furthermore, these found be highly cellular communication efficiency. Therefore, this expected new method forecasting patients' prognosis effectiveness treatment, providing insights decision-making.

Язык: Английский

Процитировано

0
Cardiac Magnetic Resonance Imaging in Immune Checkpoint Inhibitor–Related Myocarditis DOI Open Access

Matthew Hammer,

Maciej Tysarowski, Cristina Fuss

и другие.

Echocardiography, Год журнала: 2025, Номер 42(3)

Опубликована: Март 1, 2025

ABSTRACT Immune checkpoint inhibitors (ICIs) have revolutionized oncologic treatment, offering a novel and effective approach to personalized cancer immunotherapy. By targeting immune tolerance pathways, ICIs enhance T‐cell‐mediated tumor cytotoxicity. Despite their therapeutic efficacy, are associated with immune‐related adverse events (irAEs), including severe cardiovascular complications like myocarditis, pericarditis, vasculitis. ICI‐related although uncommon, carries high mortality rate of up 50%, particularly in patients receiving combination therapies. This review examines the mechanisms ICIs, highlights clinical presentation cardiac irAEs, underscores utility magnetic resonance imaging (CMR) diagnosis ICI‐associated myocarditis. Through case studies, we illustrate diagnostic strategies for complications, highlighting importance multidisciplinary collaboration mitigating morbidity mortality.

Язык: Английский

Процитировано

0
Recent advances in oncolytic virus combined immunotherapy in tumor treatment DOI Creative Commons
Xiaoli Zhou, Shunfeng Hu, Xin Wang

и другие.

Genes & Diseases, Год журнала: 2025, Номер unknown, С. 101599 - 101599

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Monoclonal antibody immune therapy response instrument for stratification and cost-effective personalized approaches in 3PM-guided pan cancer management DOI
Salem Baldi, Mohammed Alnaggar,

Maged AL-Mogahed

и другие.

The EPMA Journal, Год журнала: 2025, Номер unknown

Опубликована: Март 22, 2025

Язык: Английский

Процитировано

0
Adverse drug reaction assessment of pembrolizumab in cervical cancer treatment: a real-world pharmacovigilance study using the FAERS database DOI Creative Commons
Huiping Zhang, Zhuo Zhou,

Juan Wang

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 8, 2025

Advanced cervical cancer remains associated with high mortality rates. While pembrolizumab has improved clinical outcomes in cancer, the therapeutic efficacy advanced stages is often compromised by immune-related adverse events (irAEs). This study aimed to systematically analyze pembrolizumab-associated (AEs) using FDA Adverse Event Reporting System (FAERS) database, providing new insights for optimizing practice. AE reports related were extracted from FAERS database (Q1 2016 Q4 2024). Disproportionality analyses performed multiple algorithms, including reporting odds ratio (ROR), proportional (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). AEs classified system organ class (SOC) preferred term (PT) based on Medical Dictionary Regulatory Activities (MedDRA), then ranked frequency signal strength. A total of 646 pembrolizumab-related identified. Age distribution peaked at 45-65 years cohort (32.75%), followed 18-44 (12.85%), 66-75 (11.76%), >75 (4.64%). Among 270 documented onset timelines, predominantly occurred 3-6 months after initiation (n=114, 41.36%). Clinical categorized as other (52.80%), hospitalization (27.00%), death (10.25%), unknown (6.06%), life-threatening (2.77%), disability (1.12%). Predominant involved hematologic, endocrine, dermatologic, neurologic, gastrointestinal, urinary, reproductive systems. real-world pharmacovigilance characterizes identifying high-signal such hematologic disorders, endocrine dysfunction, dermatologic toxicities. These findings provide critical evidence risk stratification safety monitoring practice, emphasizing need organ-specific vigilance during treatment window.

Язык: Английский

Процитировано

0
A newly constructed STC2/FPR1 dual genes signature works as a prognosis risk indicator with implication in the macrophages dominated and TIM-3 checkpoint related osteosarcoma immune landscape DOI Creative Commons
Wenxia Ma, Lei Miao, Siying Liu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Abstract Background Osteosarcoma has been a common bone malignancy occurring in children and adolescents. Attributing to high tumor heterogeneity, none specific breakthrough received targeted gene therapy for osteosarcoma, although it’s still of great potential immunotherapy clinical application. In the study, 5 GEO profiles containing transcriptome information 109 osteosarcoma samples, single cell sequencing data composed 6 cases as well 43 local hospital tissue samples were combine used identify promising immune related candidate genes osteosarcoma. Methods Based on microarrays from database profile IMMPORT database, differently expressed meanwhile candidates comparing normal control identified. Then, protein-protein interaction network (PPI), survival analysis followed by LASSO succession applied construct signature based selected genes. After understanding basic genetic physicochemical properties evaluating prognosis risk association using cancer its with microenvironment features including macrophages included various cells infiltration, different checkpoints expression, signaling pathways involvement next step assessed. Results From datasets which contains total 108 level PPI highlighted cluster Further, ROC curve Cox regression assisted scaled hub down 2 key genes, namely STC2 FPR1, was constructed them. double staining immunochemistry (IHC) experiment date revealed that mainly cells, meanwhile, FPR1 mostly enriched focused also main type microenvironment. Moreover, combining STC2/FPR1 dual associated distribution multiple checkpoints, especially TIM-3. correlation between other death (ICD) ESTIMATE score additionally evaluated. Conclusions analysis, constructed. Immune indicated infiltration ans it TIM-3 expression. The results shall benefit further researches assist revealing prediction markers immunotherapy.

Язык: Английский

Процитировано

0