Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Features associated with enhanced proliferation define lung tumors that respond to dual immune checkpoint and radiation therapy

ABSTRACT: Features associated with enhanced proliferation define lung tumors that respond to dual immune checkpoint and radiation therapy

PROVIDER: PRJNA1066291 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Features associated with enhanced proliferation define lung tumors that respond to dual immune checkpoint and radiation therapy

Project description:In a randomized phase II trial, patients with early-stage non-small cell lung cancer were were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation. We conducted an analysis of the gene expression profiles of treatment-naive tumors from these patients and identified a 140-gene signature that was correlated with a positive response to the dual therapy. This signature showed enrichment in genes associated with cell proliferation.

2024-01-18 | GSE253564 | GEO

Radiation and Dual Checkpoint Blockade Activates Non-Redundant Mechanisms in Cancer

Project description:Response to immune checkpoint inhibitors may be improved through combinations with each other and other therapies, raising questions about non-redundancy and resistance. We report results from parallel studies of melanoma patients and mice treated with anti-CTLA4 and radiation (RT). Although combined treatment improved responses, resistance was common. Computational analyses of immune and transcriptomic profiles (provided here) revealed that resistance in mice was due to upregulation of tumor PD-L1 that drives T cell exhaustion. Accordingly, optimal response requires RT, anti-CTLA4, and anti-PD-L1. Anti-CTLA4 inhibits Tregs, RT diversifies and shapes the TCR repertoire, and anti-PD-L1 reinvigorates exhausted T cells. Together, all three therapies promote the expansion of clonotypes with distinct TCR traits. Similar to mice, patients with melanoma showing high PD-L1 did not respond to RT + anti-CTLA4, demonstrated persistent T cell exhaustion, and rapidly progressed. Thus, the combination of RT, anti-CTLA4, and anti-PD-L1 promotes response through distinct mechanisms.

2015-03-16 | GSE65503 | GEO

Radiation enhanced the local and distant anti-tumor efficacy in dual immune checkpoint blockade therapy in osteosarcoma.

Project description:Radiation therapy has been long utilized as localized cancer treatment. Recent studies have also demonstrated that it has a distant effect by the enhanced immunity, but it rarely occurs. The purpose of this study was to investigate whether X-ray irradiation combined with anti-PD-L1 and anti-CTLA-4 antibodies (P1C4) provides a higher probability of this distant effect as well as enhanced local antitumor efficacy for osteosarcoma. LM8 mouse osteosarcoma cells were inoculated into both legs of C3H mice assigned to one of four groups, namely no treatment (No Tx), P1C4, X-ray irradiation (RAD) to the leg of one side, and combination (COMB) groups. Survival and treatment-related immune molecular changes were analyzed. Administration of P1C4 produced a tumor growth delay on day 30 in 18% of the mice. In contrast, combination therapy produced the strongest tumor growth inhibition not only at the irradiated tumor but also at unirradiated tumor in 67% of the mice. Accordingly, lung metastasis in the COMB group was strongly reduced by 98%, with a significant survival benefit. Unirradiated tumor in mice in the COMB group significantly recruited CD8 + tumor-infiltrating lymphocytes with a moderate reduction of Treg, producing a significant increase in the CD8/Treg ratio. These results suggest that radiation enhances the efficacy of P1C4 treatment against distant metastasis as well as local control in osteosarcoma. Our data suggest that radiation therapy combined with dual checkpoint blockade may be a promising therapeutic option for osteosarcoma.

| S-EPMC5734786 | biostudies-literature

Sequential azacitidine and carboplatin can prime high-grade serous ovarian cancer to respond to checkpoint inhibitor immunotherapy

Project description:Sequential azacitidine and carboplatin can prime high-grade serous ovarian cancer to respond to checkpoint inhibitor immunotherapy

| PRJNA706585 | ENA

Sequential azacitidine and carboplatin can prime high-grade serous ovarian cancer to respond to checkpoint inhibitor immunotherapy.

Project description:Sequential azacitidine and carboplatin can prime high-grade serous ovarian cancer to respond to checkpoint inhibitor immunotherapy.

| PRJNA717226 | ENA

Clonally expanded CD38hi cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor-associated arthritis

Project description:Clonally expanded CD38hi cytotoxic CD8 T cells define the T cell infiltrate in checkpoint inhibitor-associated arthritis

| PRJNA846154 | ENA

Allelome.PRO A pipeline to define allele-specific genome features

Project description:We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. Defining allele-specific genome features from F1 E12.5 mouse embryonic fibroblasts

2015-08-03 | E-GEOD-69168 | biostudies-arrayexpress

Gene expression comparison of exhausted CD8 T cells that respond or do not respond to PD-1 blockade

Project description:CD8 T cells that respond to PD-1 blockade (during the early stage of infection) have enriched CD28 costimulation genes During the early stages of chronic infection PD-1 blockade is effective are rescuing exhausted CD8 T cells. However during the later stages of chronic infection PD-1 blockade is not able to induce a significant rescue of exhausted T cells. In order to understand the transcriptional basis of these difference we performed an RNA comparison. There is enrichment in several genes and pathways, and we hypothesize that these could be exploited for optimizing immune checkpoint therapies during the later stages of chronic infection.

2019-05-01 | GSE118201 | GEO

Expression-Based Subtypes Define Pathologic Response to Neoadjuvant Immune-Checkpoint Inhibitors in Muscle-Invasive Bladder Cancer

Project description:Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling.

| EGAS00001005549 | EGA

Hypoxia-induced alterations of G2 checkpoint regulators

Project description:Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, in addition to DNA repair, genome stability is also controlled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can alter the DNA damage cell cycle checkpoints. Here, we show that hypoxia (24h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting of U2OS cells. While some of the changes reflected hypoxia-induced inhibition of cell cycle progression, flow cytometric bar-coding analysis of individual cells showed that the levels of several G2 checkpoint regulators were reduced in G2 phase cells after hypoxic exposure, in particular cyclin B1. These effects were accompanied by decreased Cyclin dependent kinase (CDK) activity in G2 phase cells after hypoxia. Furthermore, cells pre-exposed to hypoxia showed a longer G2 checkpoint arrest upon treatment with ionizing radiation. Similar results were found following other hypoxic conditions (~0.03 % O2 20h and 0.2% O2 72h). These results demonstrate that the DNA damage G2 checkpoint can be altered as a consequence of hypoxia, and we propose that such alterations may influence the genome stability of hypoxic tumors. We measured gene expression changes in U2OS cells after treatment with 0.2% hypoxia for 24 hours. The data were used in the exploration of hyopxia induced alterations in the G2 checkpoint.

2016-01-04 | E-GEOD-70530 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data