Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

X-ray-induced more serious damage to CD8+ T cells in patients with hypopharyngeal squamous cell carcinoma (HPSCC) than those in healthy individuals

ABSTRACT: Radiotherapy (RT) is a commonly used clinical management for hypopharyngeal squamous cell carcinoma (HPSCC), which represents the most unfavorable prognosis among all subtypes of head and neck squamous cell carcinoma. However, radiation may cause lymphopenia, a significantly adverse event with detrimental prognostic implications for patients. While CD8+ T cells are vital in tumor immunity, the specific effects of RT on CD8+ T cells as well as the underlying mechanisms have not been clearly elucidated. Here we found that subpopulations of peripheral T lymphocytes exhibited differential profiles in patients with HPSCC compared to healthy individuals both pre- and post-irradiation. Importantly, CD8+ T cells from HPSCC patients showed greater reduction of cytokine production, more severe proliferation defect, and increased apoptosis compared to those of healthy individuals after in vitro irradiation. Mechanistically, ATM-Chk2 pathway mediated the attenuated radiation-induced apoptosis of CD8+ T lymphocytes from HPSCC patients. Our study demonstrated that CD8+ T cells in patients with HPSCC are more sensitive to the radiation-induced damage than those in healthy individuals. Therefore, our findings present a potential immunotherapeutic target for safeguarding CD8+ T cells against radiation-induced damage.

ORGANISM(S): Homo sapiens

PROVIDER: GSE274788 | GEO | 2024/10/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A radiation-induced gene expression signature as a tool to predict acute radiotherapy-induced adverse side effects

Project description:The majority of patients tolerate radiotherapy well, but some of them suffer from severe side effects. To find genes possibly predictive for radiosensitivity, mRNA profiles were generated before and 6 h after in vitro irradiation with 5 Gy. We analyzed lymphocytes from four head and neck and eight breast cancer patients with strong acute radiation toxicity and from 12 matching normal reacting patients in a blind study. In peripheral blood lymphocytes of all patients, 153 genes were identified which were statistically significantly altered by a fold change of more than 50% by irradiation. Pathway analysis revealed genes involved in p53 signalling, cell cycle control and apoptosis in response to radiation in primary lymphocytes. In these cells, a set of 67 radiation-induced genes was identified capable of differentiating between severe radiosensitive and normal reacting patients. More than one third of such classifying genes belong to the group of apoptosis or cell cycle regulating genes. Total RNA obtained from lymphocytes of cancer patients with strong acute radiation toxicity and from matching normal reacting patients were compared 6 hours after in vitro irradiation with 5 Gy.

2012-09-06 | E-GEOD-40640 | biostudies-arrayexpress

A radiation-induced gene expression signature as a tool to predict acute radiotherapy-induced adverse side effects

2012-09-06 | GSE40640 | GEO

Prediction of in vivo radiation dose in radiotherapy patients using ex vivo and in vivo gene expression signatures

Project description:After defining a gene expression signature that predicted radiation exposure dose with high accuracy in human peripheral white blood cells irradiated ex vivo, we now demonstrate the predictive power of gene expression signatures in blood from patients undergoing total body irradiation. Using whole genome microarray analysis, we have identified genes that respond to radiation exposure in cancer patients in vivo. A 3-nearest neighbor classifier built from these genes correctly predicted samples as exposed to 0, 1.25 or 3.75 Gy with 94% accuracy even when samples from healthy donor controls were included. The same samples were classified with 98% accuracy using a signature previously defined from ex vivo irradiation data. The samples could also be classified as exposed or not exposed with 100% accuracy using multiple methods. The demonstration that ex vivo irradiation is an appropriate model that can provide meaningful prediction of in vivo exposure, and that the signatures are robust across diverse disease states, is an important advance in the application of gene expression for biodosimetry. Translation of these signatures to a fully automated “lab-on-a-chip” device will enable high-throughput screening for large-scale radiological emergencies, as well as making such tests practical for clinical uses. Radiation induced gene expression was measured in vivo in TBI patients at 4 hours after 1.25Gy exposure or at 24 hours after 3.75Gy exposure with three 1.25Gy split doses (approximately 4 hours apart). A total of 18 TBI patients, diagnosed with a variety of cancers were used in this study. Blood from 14 healthy control individuals was also used for comparison.

2011-01-31 | E-GEOD-20162 | biostudies-arrayexpress

NanoSTRING analysis of sorted intratumoral CD8+ T cells following radiotherapy

Project description:The recruitment of monocytes and their differentiation into immunosuppressive cells is associated with the negative outcome of non-conformal radiotherapy (RT). However, non-conformal RT is irrelevant in the clinic, and little is known about the role of monocytes following radiotherapy modes used in patients, such as conformal radiotherapy (CRT). Here, we investigated the acute immune infiltration post-CRT. Contrary to non-conformal RT approaches, we found that CRT induces a rapid and robust recruitment of monocytes to the tumor that minimally differentiate into tumor-associated macrophages (TAM) or dendritic cells (DC), but instead upregulate major histocompatibility complex II (MHCII) and costimulatory molecules. We establish that these large numbers of infiltrating monocytes are responsible for increasing type I interferon in the tumor microenvironment (TME), activation of CD8+ T cells and the reduction in tumor burden. Importantly, we demonstrate that rapid monocyte infiltration to the TME is hindered when RT inadvertently affects healthy tissues. Our results unravel a positive role of monocytes during clinically relevant modes of RT and demonstrate that limiting exposure of healthy tissues to radiation has a positive therapeutic effect on the overall immune response within the tumor. The objective of this experiment was to evaluate the transcriptional changes in CD8+ T cells following different modes of radiation at 3 days post treatment

2023-05-07 | GSE207105 | GEO

X-ray-induced more serious damage to CD8+ T cells in patients with hypopharyngeal squamous cell carcinoma (HPSCC) than those in healthy individuals

Project description:X-ray-induced more serious damage to CD8+ T cells in patients with hypopharyngeal squamous cell carcinoma (HPSCC) than those in healthy individuals

| PRJNA1148058 | ENA

Radiation-induced genes expressed in two murine tumors.

Project description:Gene expression profiling was used to identify genes that display radiation-induced transcriptional change over tumor histopathology. Keywords: mouse squamous cell carcinoma, fibrosarcoma and mammary carcinoma, gamma-irradiation, carbon ion irradiation, resected sample, transplanted tissues

2009-03-20 | GSE5331 | GEO

Towards unravelling biological mechanisms behind radiation-induced oral mucositis via mass spectrometry-based proteomics

Project description:Objective: Head and neck cancer (HNC) accounts for almost 850,000 new cases per year. Radiotherapy (RT) is used to treat the majority of these patients. A common side-effect of RT-treatment is onset of oral mucositis: a painful irritation and swelling in mouth, which decreases the quality of life and is the major dose-limiting factor in RT. To understand the origin of oral mucositis, the biological mechanisms post-ionizing radiation (IR) need to be understood. This knowledge can be used to develop new treatment targets for oral mucositis and markers for the early identification of “at risk” patients. Results: Mass spectrometry-based proteomics identified 5879 proteins in primary keratinocytes and 4597 proteins in OKF6 cells. Amongst them, 212 proteins in primary keratinocytes and 169 proteins in OKF6 cells were significantly differentially abundant 96 h after 6 Gy irradiation compared to sham-irradiated controls. Protein-protein in silico enrichment predicted interferon (IFN) response and DNA strand elongation pathways as mostly affected pathways in both cell systems. Both pathways were confirmed in OKF6 cells. Immunoblot validations showed a decrease in minichromosome maintenance (MCM) complex proteins 2-7 and an increase in IFN associated proteins STAT1 and ISG15. In line with affected IFN signalling, mRNA levels of IFNβ and interleukin 6 (IL-6) increased significantly following irradiation and also levels of secreted IL-1β IL-6, IP-10, and ISG15 were elevated. Conclusion: This study has investigated biological mechanisms in keratinocytes post-in vitro ionizing radiation. A common radiation signature in keratinocytes was identified. A role of IFN response in keratinocytes along with increased levels of pro-inflammatory cytokines and proteins could hint towards a possible mechanism for oral mucositis.

2023-06-09 | PXD040398 | Pride

Rapid Monocyte Recruitment Dictates the Therapeutic Efficacy of Focal Radiotherapy

2022-06-30 | MSV000089775 | MassIVE

Transcription profiling of CD4+ T lymphocytes in response to an irradiation dose of 1 Gy.radiation

Project description:Differences in radiosensitivity existing among cells which constitute the lymphocyte population have been known for a long time, although the molecular basis of this differential radiation sensitivity remains unclear. In an attempt to get more insight into the molecular mechanisms leading to radiation effects, we used microarray analysis to study transcriptional changes in CD4+ T lymphocytes to an irradiation dose of 1 Gy. The contribution of the cell type to the radiation response of CD4+ lymphocytes was deduced by comparing our results with a gene expression profile observed in Peripheral Blood Lymphocytes published by other groups (Amundson, 2000; Kang, 2003, Jen, 2003).

2005-12-31 | E-MEXP-320 | biostudies-arrayexpress

Simultaneous targeting of PD-1 and IL2RBY with radiation therapy to inhibit pancreatic cancer growth and metastasis

Project description:In patients with pancreatic ductal adenocarcinoma (PDAC), we show that response to radiation therapy (RT) is characterized by increased IL2R and IL2R expression, decreased ILR2 and exhaustion markers. The bispecific PD-1-targeted IL-2 variant (IL2v) immunocytokine with engineered IL-2 cis-targeted to PD-1 and abolished IL2R binding targets the activation of tumor-antigen specific T cells while rescuing them from Treg suppression. Using aPD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival along with profound increase in tumor-infiltrating polyfunctional CD8 T cell subsets with a transcriptionally and metabolically active phenotype, and preferential activation of antigen-specific CD8 T cells. In combination with single dose RT, aPD1-IL2v treatment results in a robust, durable expansion of polyfunctional CD8 T cells, T cell stemness, tumor-specific memory immune response, NK cell activation, and decreased Tregs. These data show that the novel aPD1-IL2v, leads to profound local and distant response in PDAC.

2024-05-24 | PXD040266 | Pride

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