Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intratumoral radiation dose heterogeneity augments antitumor immunity in mice and primes responses to checkpoint blockade

ABSTRACT: The immunologic effects of radiation (RT) are influenced by dose and each may be optimized over a unique dose range. We hypothesized that delivering a heterogenous dose of RT would enhance anti-tumor immunity compared to homogenous RT in combination with immune checkpoint blockade (ICI). Using a point source, we delivered a spectrum of dose (~2-32 Gy) to the primary tumor and observed superior systemic immunity in models of metastatic cancer compared to low (2 Gy), moderate (8 Gy), or high (20 Gy) dose homogenous RT. Heterogeneity in RT dose resulted in spatial heterogeneity in gene expression and immune cell infiltration. Moreover, heterogenous RT optimally engaged multiple immune signaling pathways with diverse dose response relationships whereas responses to homogenous RT treatment groups were limited. Single cell RNAseq demonstrated unique enrichment of immune cell populations between each homogenous RT dose group, with several of these dose-dependent changes also represented in the heterogeneously treated tumors, with engagement of both lymphoid and myeloid compartments. This optimized activation of multiple immune mechanisms with distinct dose-dependent profiles within a single tumor may underlie a greater capacity of RT heterogeneity to augment anti-tumor immune response when combined with ICI, as compared to homogenous dose RT.

ORGANISM(S): Mus musculus

PROVIDER: GSE234159 | GEO | 2024/07/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Intratumoral radiation dose heterogeneity augments antitumor immunity in mice and primes responses to checkpoint blockade

Project description:The immunologic effects of radiation (RT) are influenced by dose and each may be optimized over a unique dose range. We hypothesized that delivering a heterogenous dose of RT would enhance anti-tumor immunity compared to homogenous RT in combination with immune checkpoint blockade (ICI). Using a point source, we delivered a spectrum of dose (~2-32 Gy) to the primary tumor and observed superior systemic immunity in models of metastatic cancer compared to low (2 Gy), moderate (8 Gy), or high (20 Gy) dose homogenous RT. Heterogeneity in RT dose resulted in spatial heterogeneity in gene expression and immune cell infiltration. Moreover, heterogenous RT optimally engaged multiple immune signaling pathways with diverse dose response relationships whereas responses to homogenous RT treatment groups were limited. Single cell RNAseq demonstrated unique enrichment of immune cell populations between each homogenous RT dose group, with several of these dose-dependent changes also represented in the heterogeneously treated tumors, with engagement of both lymphoid and myeloid compartments. This optimized activation of multiple immune mechanisms with distinct dose-dependent profiles within a single tumor may underlie a greater capacity of RT heterogeneity to augment anti-tumor immune response when combined with ICI, as compared to homogenous dose RT.

2024-07-12 | GSE234157 | GEO

Early dynamic transcriptomic changes as predictors of preoperative radiotherapy efficacy in patients with rectal cancer: a feasibility study.

Project description:With a view to developing novel biomarkers of the efficacy of radiotherapy in patients with rectal cancer, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy. Repeat biopsy did not increase toxicity. Radiotherapy induced the expression of genes involved in oxidative stress, signal transduction, apoptosis and immune response. Two rectum tumor biospsies for each patient (6 cases) : before RT and one hour after a dose of 7.2 Gy (4th fraction) during RT.

2011-12-12 | E-GEOD-26027 | biostudies-arrayexpress

Divergent outcomes of anti-PD-L1 treatment coupled with host-intrinsic differences in TCR repertoire and distinct T cell activation states in responding versus non-responding tumors

Project description:Differential responses to immune checkpoint inhibitors (ICI) may be attributed to tumor-intrinsic factors or environmental cues; however, these mechanisms cannot fully explain the variable ICI responses in different individuals. Here, we investigate the potential contribution of immunological heterogeneity with a focus on differences in T-cell receptor (TCR) repertoire to ICI responses, which has not been defined previously.

2022-10-10 | GSE214348 | GEO

Whole saliva baseline proteome profile - head and neck cancer

Project description:Oral mucositis (OM) is a common, painful and often treatment-limiting side effect of radiotherapy (RT) for head and neck cancer (HNC) patients. Unstimulated saliva was collected before the first radiotherapy application in 50 HNC patients. 41 out of 50 patients developed OM (grade III) during radiotherapy, of which 14 patients even displayed an early OM (grade III) at low radiation dose of 30 Gy. Nine patients did not develop OM (grade III). Using an LC-MS/MS approach 5,323 tryptic peptides were assigned to 487 distinct proteins (≥2 peptides) in the data set. The levels of 48 proteins differed significantly (p<0.05) between patients developing OM or not. 17 proteins displayed increased levels (≥1.3-fold) and 31 proteins decreased in level in OM, respectively. Furthermore, using partial least square analysis proteins patterns could be used to distinguish subjects which did not develop grade III OM even after 70 Gy total dose (n=9) and those displaying early OM (grade III at <30 Gy total dose, n=14). Using leave one out cross validation 37 of 41 patients (90%) developing OM could be correctly assigned indicating that prognostic proteome signatures may help to identify patients that should be specifically monitored to increase overall effectiveness of RT treatment.

2016-07-04 | PXD003230 | Pride

Proteomics analysis of primary mouse sarcomas post radiation therapy

Project description:- We revealed that inhibition of glutamine metabolism via genetic deletion or pharmacological inhibition of glutaminase (Gls1) radiosensitizes primary sarcomas in vivo. To delineate the potential mechanism(s) of radiosensitization post radiation therapy (RT), we performed proteomic analysis of Gls1+/+ and Gls1fl/flsarcomas 48 hours post 10 Gy RT. We found that 490 and 217 proteins were differentially expressed in Gls1fl/flsarcomas post 0 Gy and 10 Gy compared to Gls1+/+ sarcomas, respectively. Hallmark pathway analysis revealed that Gls1 deletion with or without RT decreased the expression of protein related to proliferation and translation (E2F targets and G2M checkpoint). Interestingly, Gls1 deletion post-RT increased innate immune response marked by elevated interferon-alpha, interferon-gamma, and natural killer (NK) cell responses. Flow cytometry analysis further validated these findings and showed significantly elevated NK cells, but not dendritic and myeloid cells in primary Gls1-deficient sarcomas compared to Gls1-proficient sarcomas post-RT. Collectively, proteomic and flow cytometry datasets suggested that innate immune response is partly accountable for radiosensitizing Gls1-deficient sarcomas.

2024-06-03 | PXD050936 | Pride

Radiation dose-fractionation effects on immune modulation in murine mammary tumors

Project description:Radiation therapy (RT) induces pleiotropic effects on the tumor immune microenvironment, but how these changes are modulated by radiation dose-fractionation is not well understood. Our in vivo data murine data suggests that while changes evoked by RT in the tumor immune compartment are largely concordant between radiation regimens, several key immunological processes are differentially regulated by radiation dose-fractionation.

2020-12-01 | GSE162418 | GEO

Data independent acquisition mass spectrometry (DIA-MS) analysis of FFPE rectal cancer samples offers in depth proteomics characterization of response to neoadjuvant chemoradiotherapy

Project description:A total of 97 LARC patients treated at the Institute for Oncology and Radiology of Serbia in the period of 2018-2019 were included in the study. Patients were treated with long-course chemoradiotherapy (CRT): Radiotherapy (RT) was delivered with a total dose of 50.4 Gy in 28 fractions; concomitant chemotherapy (5-FU, 350 mg/m2 daily) and Leucovorin (25 mg/m2 daily) was administered during the first and the fifth week of RT. Patients were evaluated in week 6-8 after treatment completion with pelvic MRI scan and rigid proctoscopy. Pathohistological response after surgery was assessed according to tumor regression grading (TRG) categories by Mandard. Twenty biopsy samples taken at diagnosis were used for proteomic analysis, 9 responders (R, TRG 1-2), and 11 non-responders (NR, TRG 3-5), in order to achieve the maximum range of different molecular features potentially associated with response.

2023-11-21 | PXD040451 | Pride

Comparison of gene expression changes in TSA tumors following different radiation regimens.

Project description:Radiotherapy is under investigation in the clinic for its ability to induce an in situ vaccine and enhance responses to immune checkpoint inhibitors and other immunotherapies. A variety of radiation doses and delivery schedules have been used to induce anti-tumor T cells in preclinical studies. However, the mechanisms bu which radiation induces anti-tumor T cells against poorly immunogenic tumors remain incompletely understood. In this study, we investigated changes in gene expression in mouse mammary carcinoma TSA tumors after a single dose (SD) of 20 Gy and a multi-fraction (MF) radiation regimen of 3x8Gy. To this end, TSA cells were injected into syngeneic BALB/c mice. When tumors became palpable, they were treated with local radiation therapy (RT) and harvested 4 or 24 hours later for gene expression analysis. The genome-wide microarray analysis showed key differences between SD and MF RT that may explain the differential ability of these two RT regimens to synergize with immune checkpoint inhibitors (Dewan et al., Clin Cancer Res 2009).

2017-06-09 | GSE83915 | GEO

Methylation cytometric pretreatment blood immune profiles with tumor mutation burden as prognostic indicators for survival outcomes in head and neck cancer patients on anti-PD-1 therapy

Project description:Tissue biomarkers for immune checkpoint inhibitor (ICI) response are limited by tumor sample heterogeneity and availability. This study identifies clinically actionable pretreatment blood biomarkers that are associated with ICI treatment response and survival in recurrent/metastatic head and neck squamous cell carcinoma. A prospective multi-center study enrolled 100 patients before standard-of-care immunotherapy. Blood immune profiles, measured by methylation cytometry, were assessed alongside tumor mutational burden (TMB) and PD-L1 combined proportion score (CPS). TMB and PD-L1 CPS were available for 56 and 91 patients, respectively. High neutrophils, monocytes, and neutrophil-to-lymphocyte ratio were associated with worse survival, while high CD4T cells, especially naïve CD4T cells, and lymphocyte-to-monocyte ratio were associated with better survival. Significant interactions between TMB and peripheral immune profiles for both progression-free and overall survival were found. Clinically relevant pretreatment peripheral immune biomarkers were identified, demonstrating the potential of DNA-based immune profiling to predict ICI response before treatment.

2024-11-15 | GSE277573 | GEO

Intratumoral diversity in Follicular lymphoma

Project description:Follicular lymphoma (FL) shows heterogenous expression of the cell surface B-cell marker, CD20. In order to investigate whether this heterogeneity also marks underlying transcriptional heterogeneity, we sorted tumor B-cells from 8 FL specimens based upon their intermediate or high expression of CD20 and transcriptionally profiled them. CD20 intermediate and CD20 high tumor B-cells were sorted by FACS, RNA extracted, and profiled using Affymetrix U133 plus 2.0 microarrays.

2013-01-01 | E-GEOD-38816 | 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