Similar Datasets
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:RNA-sequencing analysis of CD4 T cells following ipilimumab therapy
| PRJNA472360 | ENA
Project description:Metastatic uveal melanoma (UM) remains challenging to treat, with objective response rates to immune checkpoint blockade (ICB) much lower than in primary cutaneous melanoma (CM). Besides a lower mutational burden, the overall immune-excluded tumor microenvironment of UM might contribute to the poor response rate. We therefore aimed at targeting deficiency in argininosuccinate synthase 1, which is a key metabolic feature of UM. This study aimed at investigating safety and tolerability of a triple combination consisting of ipilimumab and nivolumab immunotherapy and the metabolic therapy ADI-PEG 20. 9 patients were enrolled in this pilot study. The combination therapy was safe and tolerable with absence of immune related adverse events (irAE) of special interest but with 4 of 9 patients experiencing a CTCAE grade 3 AE. No objective responses were observed. All except one patient developed anti-drug antibodies (ADA) within a month of treatment initiation and therefore did not maintain arginine depletion. Further, an IFNg-dependent inflammatory signature was observed in metastatic lesions in patients pre-treated with ICB compared with patients with no pretreatment. Multiplex immunohistochemistry demonstrated variable presence of tumor infiltrating CD8 lymphocytes and PD-L1 expression at baseline in metastases.
2022-05-13 | GSE202687 | GEO
Project description:Background: Adjuvant therapy for high-risk resected melanoma with PD-1 blockade results in median relapse-free survival (RFS) of 5 years. The addition of low dose ipilimumab (IPI) to a regimen of nivolumab (NIVO) in Checkmate-915, did not result in increased RFS. A pilot phase II adjuvant study of either standard or low dose IPI with NIVO was conducted at two centers to evaluate RFS with correlative studies. Methods: Patients (pts) with resected stages IIIB/IIIC/IV melanoma received either IPI 3mg/kg and NIVO 1mg/kg (cohort 4) or IPI 1mg/kg and NIVO 3mg/kg (cohorts 5 and 6) induction therapy every three weeks for 12 weeks, followed by maintenance NIVO. Peripheral blood samples at baseline and on-treatment were assessed by flow cytometry for potential biomarkers. Peripheral CD8+ T-cells were assessed by RNA-Seq. Results: High rates of grade 3-4 adverse events precluded completion of induction therapy in 50%, 35% and 7% of patients in cohorts 4, 5 and 6 respectively. At a median of 63.9 months of follow up, 16/56 pts (29%) relapsed. For all patients, at five-years, RFS was 71% (95% CI: 60, 84), and overall survival was 94% (95% CI: 88, 100). Expansion of CD3+CD4+CD38+CD127-GARP- T-cells, an on-treatment increase in CD39 expression in CD8+ T-cells, and T-cell expression of phosphorylated STAT2 and STAT5 were associated with relapse. Conclusions: Adjuvant IPI/NIVO at the induction doses used resulted in excellent relapse-free survival, albeit with a high rate of grade 3-4 adverse events. Biomarker analyses highlight an association of ectoenzyme-expressing T-cells and STAT signaling pathways with relapse.
2022-12-02 | GSE219251 | GEO
Project description:Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab
| PRJNA379764 | ENA
Project description:Pre-treatment (PT) and On-Treatment (C3D8) biopsy samples from patients on the Phase I trial of Ipilimumab and Evofosfamide (NCT03098160) were analyzed by RNA sequencing.
2021-06-09 | GSE159237 | GEO
Project description:Pilot Trial of Arginine Deprivation plus Nivolumab and Ipilimumab in Patients with Metastatic Uveal Melanoma
| PRJNA836946 | ENA
Project description:The ETCTN 10026 study tested decitabine and ipilimumab for transplant-naive advanced myelodysplastic syndrome/acute myeloid leukemia and relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Using single cell RNA sequencing, determinants of response (higher T/NK to myeloid cell ratio in responders) and resistance (insufficient clearance of AML clones) were identified and pharmacodynamics of decitabine (cytoreduction) and ipilimumab (increase in regulatory T cells) characterized.
2023-10-31 | GSE223844 | GEO
Project description:The blossom of immunotherapy in melanoma highlights the need to delineate mechanisms of immune resistance. Recently, we have demonstrated that the RNA editing protein, adenosine deaminase acting on RNA-1 (ADAR1) is down-regulated during metastatic transition of melanoma, which enhances melanoma cell proliferation and tumorigenicity. Here we investigate the role of ADAR1 in melanoma immune resistance. Importantly, knockdown of ADAR1 in human melanoma cells induces resistance to tumor infiltrating lymphocytes in a cell contact-dependent mechanism. We show that ADAR1, in an editing-independent manner, regulates the biogenesis of miR-222 at the transcription level and thereby Intercellular Adhesion Molecule 1 (ICAM1) expression, which consequently affects melanoma immune resistance. ADAR1 thus has a novel, pivotal, role in cancer immune resistance. Corroborating with these results, the expression of miR-222 in melanoma tissue specimens was significantly higher in patients who had no clinical benefit from treatment with ipilimumab as compared to patients that responded clinically, suggesting that miR-222 could function as a biomarker for the prediction of response to ipilimumab. These results provide not only novel insights on melanoma immune resistance, but also pave the way to the development of innovative personalized tools to enable optimal drug selection and treatment. 13 formalin fixed paraffin embedded (FFPE) melanoma tissues were stained with hematoxilin and eosin for examination by an expert pathologist. Non-tumor tissue was removed. Total RNA was isolated using miRNeasy FFPE kit (Qiagen) according to the manufacture guidelines.
2015-12-31 | E-GEOD-67496 | biostudies-arrayexpress
Project description:Expression profiling of tumor samples obtained during CA209-038 (ClinicalTrials.gov Identifier: NCT01621490). The purpose of this study is to evaluate pharmacodynamic changes of nivolumab and nivolumab in combination with ipilimumab treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced). Samples are rumor core needle biopsies obtained at trial enrolment (i.e. Screen) and/or at Cycle 1 Day 29 (i.e.Week 4) from Subjects With Advanced Melanoma (Unresectable or Metastatic) treated with nivolumab (BMS-936558,MDX-1106) 3 mg/kg solution intravenously every 2 weeks on Bristol-Myers Squibb clinical trial protocol CA209-038 Part 1 . Cohort 2 patients have progressed on anti-CTLA4 (ipilimumab) monoclonal antibody therapy. Values are from an interim lock of the trial data in July 2014. Best overall response (BOR) was defined using RECIST 1.1 criteria: tumor assessments between date of first dose and the date of first objectively documented progression, or the date of non-missing subsequent anti-cancer therapy (whichever occurs first) were used to derive BOR. MPCT is Maximum reduction in tumor size (index lesions only) up to first progression, and is the value typically shown on a waterfall plot.
2022-01-01 | E-MTAB-4030 | biostudies-arrayexpress