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

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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.

Language: Английский

Drug combination assays using Caenorhabditis elegans as a model system DOI
Guillermina Hernando, Cecilia Bouzat

Journal of Pharmacological and Toxicological Methods, Journal Year: 2025, Volume and Issue: 131, P. 107583 - 107583

Published: Jan. 23, 2025

Language: Английский

Citations

2
Targeting GDF15 to enhance immunotherapy efficacy in glioblastoma through tumor microenvironment-responsive CRISPR-Cas9 nanoparticles DOI Creative Commons
Cheng Zou, Xiao Liu, Weizhong Wang

et al.

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

Published: Feb. 20, 2025

Despite the outstanding clinical success of immunotherapy, its therapeutic efficacy in glioblastoma (GBM) is still limited. To identify critical regulators GBM immunity, we constructed a mouse single-guide RNA (sgRNA) library corresponding to all disease-related immune genes, and performed an vivo CRISPR knockout (KO) screen syngeneic models. We demonstrated that deletion GDF15 cells ameliorated immunosuppressive tumor microenvironment (TME) enhanced antitumor checkpoint blockade (ICB) response. Moreover, designed unique nanoparticles for efficient encapsulation CRISPR-Cas9, noninvasive brain delivery cell targeting, demonstrating effective safe strategy gene therapy. The CRISPR-Cas9 nanoparticles, known as ANPSS (Cas9/sgRNA), are easily created by enclosing single Cas9/sgRNA complex polymer shell sensitive glutathione. This also contains dual-action ligand aids crossing blood‒brain barrier, targeting cells, selectively releasing Cas9/sgRNA. Our encapsulating promising resulting high editing efficiency within tumors while showing minimal off-target high-risk tissues. Treatment with (Cas9/sgGDF15) effectively halted growth, reversed suppression, ICB These results emphasize potential role modulating enhancing effectiveness current immunotherapy strategies GBM. 1. In screens driver escape. 2. Synthesis TME-responsive 3. therapy enhances

Language: Английский

Citations

0
An engineered PD1-Fc fusion produced in N. benthamiana plants efficiently blocks PD1/PDL1 interaction DOI Creative Commons
Shiva Izadi, Rafaela Abrantes,

Simon Gumpelmair

et al.

Plant Cell Reports, Journal Year: 2025, Volume and Issue: 44(4)

Published: March 22, 2025

Abstract Key message Plant-made PD1–Fc fusions engineered for optimized glycosylation and Fc-receptor engagement are highly efficient in blocking PD1/PDL1 interactions can be cost-effective alternatives to antibody-based immune checkpoint inhibitors. Immune inhibitors (ICIs) antibodies receptors that have pivotal roles during T-cell activation processes. The programmed cell death 1 (PD1) regarded as the primary targeting PD1 or its ligand PDL1 revolutionized immunotherapy of cancer. However, majority patients fail respond, treatment resistance well immune-related adverse events commonly associated with this therapy. Alternatives ICIs pathway may bear potential overcome some these shortcomings. Here, we used a plant expression platform based on tobacco relative Nicotiana benthamiana generate immunoglobulin fusion proteins harboring wild type an affinity-enhanced ectodomain. We exploited versatility our system variants differed regarding their profile capability engage Fc-receptors. Unlike wild-type counterpart, versions showed strongly augmented capabilities both protein- cell-based assays. Moreover, contrast clinical antibodies, binding is not affected by status PDL1. Importantly, could demonstrate plant-made inhibitory signaling T reporter assay. Taken together, study highlights utility plant-based protein biologics therapeutic potential. Targeting derived reduce overstimulation therapies while retaining favorable features such long serum half-life.

Language: Английский

Citations

0
Ganoderma atrum polysaccharide inhibits ROS/NLRP3/pyroptosis axis by fixing mitochondrial dynamics disorder in PD-1 inhibitors-induced carditis of Lewis lung carcinoma mice DOI

Xiaoyu Mu,

Sheng-bin Chen,

Song-yu Yang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143163 - 143163

Published: April 1, 2025

Language: Английский

Citations

0
NK/DC crosstalk-modulating antitumor activity via Sema3E/PlexinD1 axis for enhanced cancer immunotherapy DOI
Awais Ali, Abdulaziz Alamri,

Azraida Hajar

et al.

Immunologic Research, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 5, 2024

Language: Английский

Citations

3
The immune factors have complex causal regulation effects on kidney stone disease: a mendelian randomization study DOI Creative Commons

Dongfeng Yuan,

Junyi Yang,

Weisong Wu

et al.

BMC Immunology, Journal Year: 2024, Volume and Issue: 25(1)

Published: June 14, 2024

Abstract Purpose Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships yet to be established. The purpose this paper is elucidate association between and KSD by Mendelian randomization (MR) analysis. Methods In our study, a thorough two-sample analysis was performed us determine relationship cell traits disease. We included total four (median fluorescence intensity (MFI), relative cellular (RC), absolute (AC), morphological parameters (MP)), which are publicly available data. GWAS summary data related (9713 cases 366,693 controls) were obtained from FinnGen consortium. primary MR method Inverse variance weighted. Cochran’s Q test, Egger, MR-Pleiotropy RESidual Sum Outlier (MR-PRESSO) used assess stability results. Results After FDR correction, CD8 HLA DR + CD8br (OR = 0.95, 95% CI 0.93–0.98, p-value 7.20 × 10 − 4 , q-value 0.088) determined distinctly associated with KSD, we also found other 25 suggestive associations 13 suggested as protective factors 12 risk factors. There no horizontal pleiotropy or significant heterogeneity in analysis, results Cochrane Q-test, Egger’s intercept MR-PRESSO, all > 0.05. Conclusions Our study has explored connection thus providing some insights for future clinical studies.

Language: Английский

Citations

2
Programmable Bionanomaterials for revolutionizing cancer immunotherapy DOI
Ayushi Sharma, Dhiraj Bhatia

Biomaterials Science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Cancer immunotherapy involves a cutting-edge method that utilizes the immune system to detect and eliminate cancer cells.

Language: Английский

Citations

1
Progression of the Immune Escape Mechanism in Tumors DOI Creative Commons
Sheila Spada, Sumit Mukherjee

Biology, Journal Year: 2024, Volume and Issue: 13(11), P. 898 - 898

Published: Nov. 4, 2024

There exists a long-standing research interest to understand the molecular and signaling interactions between tumor cells innate adaptive immune such as dendritic cells, macrophages, NK B T that occur in microenvironment (TME) [...]

Language: Английский

Citations

1
Subverting Attachment to Prevent Attacking: Alteration of Effector Immune Cell Migration and Adhesion as a Key Mechanism of Tumor Immune Evasion DOI Creative Commons
Marta Mastrogiovanni, Emmanuel Donnadieu, Rajiv Pathak

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(11), P. 860 - 860

Published: Oct. 24, 2024

Cell adhesion regulates specific migratory patterns, location, communication with other cells, physical interactions the extracellular matrix, and establishment of effector programs. Proper immune control cancer strongly depends on all these events occurring in a highly accurate spatiotemporal sequence. In response to cancer-associated inflammatory signals, cells navigating bloodstream shift from their patrolling exploratory migration mode establish adhesive vascular endothelial cells. This interaction enables them extravasate through blood vessel walls access site. Further within tumor microenvironment (TME) are crucial for coordinating distribution situ mounting an effective anti-tumor response. this review, we examine how alterations cues context favor escape by affecting cell infiltration trafficking TME. We discuss mechanisms which tumors directly modulate patterns affect immunity evasion. also explore indirect that involve modifications TME characteristics, such as vascularization, immunogenicity, structural topography. Finally, highlight significance aspects designing more drug treatments cellular immunotherapies.

Language: Английский

Citations

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

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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.

Language: Английский

Citations

0