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Immune Signatures and Tumor Biomarkers from Whole Transcriptome Sequencing Predict Outcome in Recurrent Resectable Stage III and IV Melanoma when Evaluated Following Treatment with Hu14.18-IL2

ABSTRACT: Immune Signatures and Tumor Biomarkers from Whole Transcriptome Sequencing Predict Outcome in Recurrent Resectable Stage III and IV Melanoma when Evaluated Following Treatment with Hu14.18-IL2

PROVIDER: PRJNA552307 | ENA |

REPOSITORIES: ENA

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Immune Signatures and Tumor Biomarkers from Whole Transcriptome Sequencing Predict Outcome in Recurrent Resectable Stage III and IV Melanoma when Evaluated Following Treatment with Hu14.18-IL2

Project description:We analyzed whole transcriptome sequencing in tumors from 23 patients with stage III or IV melanoma from a pilot trial of the anti-GD2 immunocytokine, hu14.18-IL2, in melanoma patients at high risk for recurrence to identify predictive immune and/or tumor biomarkers. Patients with advanced resectable melanoma were randomized to receive the first of 3 monthly-courses of hu14.18-IL2 immunotherapy either before (Group A) or after (Group B) complete surgical resection of all known disease. Tumors were evaluated by histology, immunohistochemistry and whole transcriptome sequencing. We report here that tumor infiltrating lymphocyte (TIL) levels directly correlate with relapse-free-survival (RFS) and overall-survival (OS). Resected tumors from Group A, but not Group B, patients demonstrated a direct correlation between TIL levels and survival. TIL levels directly correlated with a previously Estimated RNAseq-determined Immune Signature (EIS). This EIS correlated with RFS and OS, particularly in Group A tumors. Group A tumors demonstrated decreased cell cycling RNA gene transcripts, but increased RNA gene transcripts associated with repair and growth. Additionally, we found several direct correlations of immune signatures and immune related RNA transcripts as well as many inverse correlations of tumor growth-associated transcripts with RFS and OS, particularly in Group A tumors. Most of these correlations were not seen in Group B tumors. We interpret these data to signify that both immunologic and tumoral cell processes, as measured by RNAseq analyses, are associated with long term survival after hu14.18-IL2 therapy and could potentially be prognosticated using neoadjuvant treatment resection specimens obtained after initiating immunotherapy.

2020-07-01 | GSE133713 | GEO

Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated After Starting Hu14.18-IL2 Predicts Outcome

Project description:Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated After Starting Hu14.18-IL2 Predicts Outcome

| PRJNA595008 | ENA

Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated After Starting Hu14.18-IL2 Predicts Outcome

Project description:Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated After Starting Hu14.18-IL2 Predicts Outcome

| PRJNA595009 | ENA

Project description:PurposeWe analyzed whole transcriptome sequencing in tumors from 23 patients with stage III or IV melanoma from a pilot trial of the anti-GD2 immunocytokine, hu14.18-IL2, to identify predictive immune and/or tumor biomarkers in patients with melanoma at high risk for recurrence.Experimental designPatients were randomly assigned to receive the first of three monthly courses of hu14.18-IL2 immunotherapy either before (Group A) or after (Group B) complete surgical resection of all known diseases. Tumors were evaluated by histology and whole transcriptome sequencing.ResultsTumor-infiltrating lymphocyte (TIL) levels directly associated with relapse-free survival (RFS) and overall survival (OS) in resected tumors from Group A, where early responses to the immunotherapy agent could be assessed. TIL levels directly associated with a previously reported immune signature, which associated with RFS and OS, particularly in Group A tumors. In Group A tumors, there were decreased cell-cycling gene RNA transcripts, but increased RNA transcripts for repair and growth genes. We found that outcome (RFS and OS) was directly associated with several immune signatures and immune-related RNA transcripts and inversely associated with several tumor growth-associated transcripts, particularly in Group A tumors. Most of these associations were not seen in Group B tumors.ConclusionsWe interpret these data to signify that both immunologic and tumoral cell processes, as measured by RNA-sequencing analyses detected shortly after initiation of hu14.18-IL2 therapy, are associated with long-term survival and could potentially be used as prognostic biomarkers in tumor resection specimens obtained after initiating neoadjuvant immunotherapy.

| S-EPMC7334053 | biostudies-literature

Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma.

Project description:Phase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5 mg/m2/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6 mg/m2/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary objectives were to: (1) evaluate histological evidence of anti-tumor activity and (2) evaluate recurrence-free survival (RFS) and OS. Twenty melanoma patients were randomized to Group A (11 patients) or B (9 patients). Two Group B patients did not receive IC due to persistent disease following surgery. Six of 18 IC-treated patients remained free of recurrence, with a median RFS of 5.7 months (95% confidence interval (CI) 1.8-not reached). The 24-month RFS rate was 38.9% (95% CI 17.5-60.0%). The median follow-up of surviving patients was 50.0 months (range: 31.8-70.4). The 24-month OS rate was 65.0% (95% CI 40.3-81.5%). Toxicities were similar to those previously reported. Exploratory tumor-infiltrating lymphocyte (TIL) analyses suggest prognostic value of TILs from Group A patients. Prolonged tumor-free survival was seen in some melanoma patients at high risk for recurrence who were treated with IC.

| S-EPMC6168354 | biostudies-literature

Transcriptomic profiling of cultured CD8+ T cells from mice and treated with either IL2, IL2/SIINFEKL(TCR), IL2/IL4, or IL2/IL4/SIINFEKL(TCR)

Project description:Transcriptomic profiling of cultured CD8+ T cells from mice and treated with either IL2, IL2/SIINFEKL(TCR), IL2/IL4, or IL2/IL4/SIINFEKL(TCR)

| PRJNA432162 | ENA

Molecular profiling of cultured CD8+ T cells from mice and treated with either IL2, IL2/SIIKFEKL(TCR), IL2/IL4, or IL2/IL4/SIINFEKL(TCR)

Project description:Molecular profiling of cultured CD8+ T cells from mice and treated with either IL2, IL2/SIIKFEKL(TCR), IL2/IL4, or IL2/IL4/SIINFEKL(TCR)

| PRJNA429800 | ENA

Salivary microRNAs May Be A Valuable Biomarker To Detect Resectable Pancreatic Cancer

Project description:Early surgery is vital in the treatment of highly fatal pancreatic cancer (PC). But there is no valuable and non-invasive biomarker to screen PC currently. Studies showed many salivary molecules can detect several systemic diseases. We aimed to investigate whether salivary microRNAs (miRNAs) can act as a biomarker to detect resectable PC. By Agilent microarray salivary miRNAs were profiled from saliva samples from 8 patients with resectable PC and 8 healthy controls. Candidate biomarkers discovered from the profile were subjected to validation by qPCR.

2013-12-15 | E-GEOD-53325 | biostudies-arrayexpress

resting and IL2 activated human natural killer cells

Project description:The aim of the study was to investigate the activation of human NK cells by IL2 through analyzing the global gene expression at different time points (0, 2, 8 and 24 hours) after culture with the cytokine IL2 at 100 IU/ml. NK cells with the CD56+/CD16+ and CD3- phenotype were negatively selected by immunomagnetic beads and re-examined by flow-cytometry to ensure greater than 90% purity . Keywords: resting and IL2 activated NK cells(time series)

2007-08-07 | GSE8059 | GEO

Towards a mechanistic understanding of response to SBRT by patients with borderline resectable pancreatic cancer

Project description:Five year survival rates for pancreatic cancer remain low, around 11%. We assessed differential gene expression between SBRT responders and non-responders as well as expression pre and post SBRT. Samples were obtained from the University of Colorado biorepository. All patients had borderline resectable pancreatic cancer, treated with neoadjuvant chemotherapy followed by restaging, and treatment with 30–33.6 Gy SBRT to pancreatic tumors, followed by pancreaticoduodenectomy and adjuvant chemotherapy. We observed increases in PDL1, PD1, CD25, and a decrease in CD122 expression following RT. Furthermore, we found that responders to SBRT exhibit decrased CD25 expression with increased CD122 and CD132 expression compared to non-responders. Using GSEA of responders vs. non-responders, we found responders to SBRT exhibit enrichment of inflammatory response, IFN signaling, and IL2/STAT5 signaling.

2023-04-20 | GSE225767 | GEO

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