Ontology highlight
ABSTRACT:
PROVIDER: PRJNA477854 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7426640_1.fastq.gz | Fastqsanger.gz | |||
| SRR7426640_2.fastq.gz | Fastqsanger.gz | |||
| SRR7426650_1.fastq.gz | Fastqsanger.gz | |||
| SRR7426650_2.fastq.gz | Fastqsanger.gz | |||
| SRR7426660_1.fastq.gz | Fastqsanger.gz |
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Project description:Introduction: Immune checkpoint inhibitors(ICIs) targeting programmed cell death protein 1 (PD1) confer significant survival benefits to patients with non-small cell lung cancer (NSCLC). However, there remains a substantial unmet need to identify therapeutic approaches to overcome resistance and provide benefits to these patients. High-dose ascorbic acid (AA) acts synergistically with many standard anticancer treatments. However, little is known about the effect of high-dose AA on improving the efficacy of anti-PD1 inhibitors in NSCLC. This study aimed to elucidate the effects of high-dose AA on anti-PD1 immunotherapy in NSCLC. Methods: The combined effects of high-dose AA and anti-PD1 were investigated using a coculture model of H460 cells and CD8+ T cells and an LLC1 lung cancer syngeneic mouse model. To investigate the molecular mechanism, tumor tissues from mice were analyzed by comprehensive proteomic profiling using nano-LC-ESI-MS/MS. Results: Pretreatment with a high dose of AA led to enhanced the sensitivity to the cytotoxicity of CD8+ T cells derived from healthy donor for H460 cells. Additionally, the combination of anti-PD1 and high-dose AA significantly increased CD8+ T cell cytotoxicity in H460 cells. The combination of anti-PD1 and high-dose AA showed dramatic antitumor effects in a syngeneic mouse model of lung cancer by significantly reducing tumor growth and increasing CD8+ T cell-dependent cytotoxicity and macrophage activity. Comprehensive protein analysis confirmed that high-dose AA in anti-PD1-treated tumor tissues enhanced the antitumor effects by regulating various immune-related mechanisms, including the B cell and T cell receptor signaling pathways, Fc gamma R-mediated phagocytosis, and natural killer (NK) cell-mediated cytotoxicity. Discussion: Our results suggest that high-dose AA may be a promising adjuvant to potentiate the efficacy of anti-PD1 immunotherapy.
2025-01-15 | PXD059688 | Pride
Project description:We created new mouse mammary tumor models to identify biomarkers of sensitivity to immune checkpoint inhibitors. Using these models in a syngeneic transplant system and treating with anti-PD1/anti-CTLA4 combination therapy, we profiled treated and non-treated tumors by RNA-SEQ. Herein, the profiled tumors represent models that are resistant or senstitive to immune checkpoint inhibitors at distinct timepoints of therapy and tumor progression.
2019-11-13 | GSE124821 | GEO
Project description:We designed a study to investiagate chemo-immunotheraputic effect using a mouse model of colon cancer. To investigate the anti-tumor effect of the combination therapy, the in vivo antitumor activities of different mono- and combinational therapy were subsequently evaluated using a C57BL/6J mouse model bearing MC38 tumors. Subcutaneous injection of 1×106 of MC38 cells in the right flank of a mouse was performed 9 days before therapy. The Ru-PD-L1 was administrated by intraperitoneal injection, while the DPD or DOX was given by peritumoral injection. For combinational treatment, each mouse was treated with 14 µg DPD or DOX (0.56 mg/kg) 6 hours after administering 20 ug Ru-PD-L1 (0.80mg/kg). For monotherapy, each mouse was treated with Ru-PD-L1, DPD, or DOX alone. On the 20th day, the mice were sacrificed for tumor collection. The results highlighted that the combination of ACC and DOX prodrug synergistically enhanced immune response and higher antitumor activity compared to the ACC and DOX combination.
2023-05-31 | GSE208721 | GEO
Project description:We previously generated a syngeneic preclinical model of NSCLC (p53R172HΔg/+KrasLA1/+) with acquired resistance to anti-PD1. In the current study, we investigated methylation differences in specific genomic regions comparing anti-PD1-resistant tumors (344SQR) with their parental-tumor counterparts (344SQP).
2020-08-17 | GSE154993 | GEO
Project description:In this comprehensive study, the authors have developed concise models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 Immune Checkpoint Blockade (ICB) treatment in individual tumors. It's important to note that their validation was performed in smaller, independent cohorts, constrained by data availability. The authors have developed two Logistic Regression based models for Ipilimumab treated and Ipilimumab naive patients with metastatic melanoma. The main predictive features for the Ipilimumab treated patients are MHC-II HLA, LDH at treatment initiation and the presence of lymph node metastases (LN met), chosen using forward selection methodology. The main predictive features for the Ipilimumab naive patients are tumor heterogeneity, tumor ploidy and tumor purity, chosen using forward selection methodology.
Please note that in these models, the output ‘1’ means progressive disease (PD) and ‘0’ means non-PD. The original GitHub repository can be accessed at https://github.com/vanallenlab/schadendorf-pd1
2023-11-17 | MODEL2310150001 | BioModels
Project description:Lenvatinib is an effective drug in advanced hepatocellular carcinoma (HCC). Its combination with the anti-PD1 immune checkpoint inhibitor pembrolizumab has achieved encouraging results in phase Ib and is currently being tested in phase III trials. Here, we aimed at exploring the molecular and immunomodulatory effects of lenvatinib alone or in combination with anti-PD1. We generated a syngeneic model of HCC in C57BL/6J mice and randomized the animals to receive placebo, lenvatinib, anti-PD1 or combination treatment. Transcriptomic analysis were performed to assess the expression profile of tumors from mice receiving each treatment strategy.
2023-04-07 | GSE153203 | GEO
Project description:The first clinical trial testing the combination of targeted therapy with a BRAF inhibitor vemurafenib and immunotherapy with a CTLA-4 antibody ipilimumab was terminated early due to significant liver toxicities, possibly due to paradoxical activation of the MAPK pathway by BRAF inhibitors in tumors with wild type BRAF. MEK inhibitors can potentiate the MAPK inhibition in tumor, while potentially alleviating the unwanted paradoxical MAPK activation. With a mouse model of syngeneic BRAFV600E driven melanoma (SM1), we tested whether the addition of the MEK inhibitor trametinib would enhance the immunosensitization effects of the BRAF inhibitor dabrafenib. Combination of dabrafenib and trametinib with pmel-1 adoptive cell transfer (ACT) showed complete tumor regression. Bioluminescent imaging and tumor infiltrating lymphocyte (TIL) phenotyping showed increased effector infiltration to tumors with dabrafenib, trametinib or dabrafenib plus trametinib with pmel-1 ACT combination. Intracellular IFN gamma staining of the TILs and in vivo cytotoxicity studies showed trametinib was not detrimental to the effector functions in vivo. Dabrafenib increased tumor associated macrophages and T regulatory cells (Tregs) in the tumors, which can be overcome by addition of trametinib. Microarray analysis revealed increased melanoma antigen, MHC expression, and global immune-related gene upregulation with the triple combination therapy. Given the up-regulation of PD-L1 seen with dabrafenib and/or trametinib combined with antigen specific ACT, we tested the triple combination of dabrafenib, trametinib with anti-PD1 therapy, and observed superior anti-tumor effect to SM1 tumors. Our findings support the testing of these combinations in patients with BRAFV600E mutant metastatic melanoma. SM1 tumors were implanted into C57BL/6 mice. Mice were treated by ACT of pmel-1 splenocytes or C57BL/6 splenocytes as control. Pmel-1 treated mice were additionally treated with either vehicle, dabrafenib, trametinib, or combination of both drugs and control mice were treated with vehicle or combination of both drugs.
2014-12-12 | E-GEOD-64102 | biostudies-arrayexpress
Project description:We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we developed clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduced tumor burden, prolonged survival, remodeled the TME, increased intratumoral T cell and natural killer (NK) cell infiltration, and induced epitope spreading. CAR-M therapy protected against antigen-negative relapse in a T cell dependent fashion, confirming long-term anti-tumor immunity. In HER2+ solid tumors resistant to anti-PD1(aPD1) monotherapy, the combination of CAR-M and aPD1 significantly improved tumor growth control, survival, and remodeling of the TME. These results demonstrate synergy between CAR-M and T cell checkpoint blockade and provide a strategy to enhance response to aPD1 therapy for patients with non-responsive tumors.
2024-11-20 | GSE275417 | GEO
Project description:We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we developed clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduced tumor burden, prolonged survival, remodeled the TME, increased intratumoral T cell and natural killer (NK) cell infiltration, and induced epitope spreading. CAR-M therapy protected against antigen-negative relapse in a T cell dependent fashion, confirming long-term anti-tumor immunity. In HER2+ solid tumors resistant to anti-PD1(aPD1) monotherapy, the combination of CAR-M and aPD1 significantly improved tumor growth control, survival, and remodeling of the TME. These results demonstrate synergy between CAR-M and T cell checkpoint blockade and provide a strategy to enhance response to aPD1 therapy for patients with non-responsive tumors.
2024-12-22 | GSE285188 | GEO
Project description:Tumors arise and grow despite anti-cancer immune responses. These responses can be stimulated by immunotherapies such as immune checkpoint inhibitors (e.g. anti-PD1 antibodies) and chimeric antigen receptors (CAR). Efficacy of these agents in solid tumors including colorectal cancers (CRC) is limited by immunosuppressive tumor microenvironment (TME) that prevents killing of malignant cells by cytotoxic T lymphocytes (CTL). Understanding the nature of TME-generated immunosuppression is of paramount importance. Here we report that TME elicited immunosuppression via eliminating activated CTL; this elimination required TME stress-induced downregulation of the IFNAR1 chain of type I interferon (IFN) receptor and attenuation of its signaling. Downregulation of IFNAR1 was observed in human colorectal cancers (CRC) and in mouse CRC models where it was required for efficient tumor development and progression. Stabilization of IFNAR1 on CTL improved their survival and increased anti- tumor activities of CAR T cells and PD1 inhibitors thereby providing a rationale for targeting IFNAR1 degradation for immunotherapies optimization. Two genotypes of mice were examined either 9 or 21 days post injection of MC38 colon cancer cells or MC38mRFP cells, respectively. 2-3 replicate mice were analyzed on separate arrays for each condition. 6 conditions in total were analyzed.
2016-01-15 | E-GEOD-76889 | biostudies-arrayexpress