NanoSTRING analysis of sorted monocytes/monoACT cells following radiotherapy
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ABSTRACT:
PROVIDER: PRJNA925928 | ENA |
REPOSITORIES: ENA
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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 evaulate the transcriptional changes in monocytes following different modes of radiation at 3 days post treatment
2023-05-07 | GSE223400 | GEO
Project description:NanoSTRING analysis of sorted intratumoral CD8+ T cells following radiotherapy
| PRJNA853748 | ENA
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
Project description:We investigated the innate immune system in the SOD1 ALS model. We found that splenic Ly6CHi monocytes were activated and their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We found a decrease in resident microglia in the spinal cord with disease progression. Two months prior to disease onset, splenic Ly6CHi monocytes had an M1 signature which included increased CCR2. At one month prior to disease onset, microglia expressed increased CCL2 and other chemotaxis-associated molecules. Microglia derived from the spinal cord of SOD1 mice recruited Ly6C+ monocytes to the CNS. Treatment with anti-Ly6C mAb modulated the Ly6CHi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss and extended survival. In humans with ALS, CD14+/CD16- monocytes (analogue of Ly6CHi monocytes) exhibited an ALS specific microRNA inflammatory signature similar to that observed in the SOD1 mouse providing a direct link between the animal model and the human disease. Thus, the SOD1-like profile of monocytes in ALS subjects may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach This study used the NanoString nCounter hybridization system and the Nanostring GX Human Immunology and Nanostring Human Inflammation assays to identify and quantitate immune-related genes in blood CD14+CD16- monocytes from ALS, MS and HC subjects Total RNA was isolated from FACS sorted CD14+CD16- blood-derived monocytes from sporadic sALS (n=10), fALS (n=4) and HC (n=10) subjects. RNA was profiled using the Nanostring GX Human Immunology and Nanostring Human Inflammation assays
2012-07-25 | E-GEOD-39642 | biostudies-arrayexpress
Project description:We investigated the innate immune system in the SOD1 ALS model. We found that splenic Ly6CHi monocytes were activated and their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We found a decrease in resident microglia in the spinal cord with disease progression. Two months prior to disease onset, splenic Ly6CHi monocytes had an M1 signature which included increased CCR2. At one month prior to disease onset, microglia expressed increased CCL2 and other chemotaxis-associated molecules. Microglia derived from the spinal cord of SOD1 mice recruited Ly6C+ monocytes to the CNS. Treatment with anti-Ly6C mAb modulated the Ly6CHi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss and extended survival. In humans with ALS, CD14+/CD16- monocytes (analogue of Ly6CHi monocytes) exhibited an ALS specific microRNA inflammatory signature similar to that observed in the SOD1 mouse providing a direct link between the animal model and the human disease. Thus, the SOD1-like profile of monocytes in ALS subjects may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach. This study used the NanoString nCounter hybridization system and nCounter miRNA expression assays to identify and quantitate miRNAs in blood CD14+CD16- monocytes from ALS, MS and HC subjects Total RNA was isolated from FACS sorted CD14+CD16- blood-derived monocytes from sporadic ALS (n=8), MS (n=8) and HC (n=8) subjects. RNA was profiled using the NanoString nCounter miRNA expression assay
2012-07-25 | E-GEOD-39643 | biostudies-arrayexpress
Project description:We investigated the innate immune system in the SOD1 ALS model. We found that splenic Ly6CHi monocytes were activated and their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We found a decrease in resident microglia in the spinal cord with disease progression. Two months prior to disease onset, splenic Ly6CHi monocytes had an M1 signature which included increased CCR2. At one month prior to disease onset, microglia expressed increased CCL2 and other chemotaxis-associated molecules. Microglia derived from the spinal cord of SOD1 mice recruited Ly6C+ monocytes to the CNS. Treatment with anti-Ly6C mAb modulated the Ly6CHi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss and extended survival. In humans with ALS, CD14+/CD16- monocytes (analogue of Ly6CHi monocytes) exhibited an ALS specific microRNA inflammatory signature similar to that observed in the SOD1 mouse providing a direct link between the animal model and the human disease. Thus, the SOD1-like profile of monocytes in ALS subjects may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach This study used the NanoString nCounter hybridization system and the Nanostring GX Human Immunology and Nanostring Human Inflammation assays to identify and quantitate immune-related genes in blood CD14+CD16- monocytes from ALS, MS and HC subjects
2012-07-26 | GSE39642 | GEO
Project description:Ablative RT results in increased expression of CCL2 within the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) and also increased recruitment of CD45+CD11b+Ly6Chi inflammatory monocytes/macrophages. This increase in CCL2 expression and recruitment of inflammatory monocytes/macrophages is a mechanism of resistance to the anti-tumor effects of ablative radiotherapy (RT). We used microarrays to study changes in gene expression patterns of inflammatory monocytes/macrophages sorted from the tumor microenvironment after ablative RT in a subcutenous model of pancreatic adenocarcinoma. From this, we identified 8 genes with an absolute fold change of expression equal to or greater than 2 with a false discovery rate equal to or less than 25 %.
2016-08-01 | GSE82276 | GEO
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.
2022-06-30 | MSV000089775 | MassIVE
Project description:Ablative RT results in increased expression of CCL2 within the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) and also increased recruitment of CD45+CD11b+Ly6Chi inflammatory monocytes/macrophages. This increase in CCL2 expression and recruitment of inflammatory monocytes/macrophages is a mechanism of resistance to the anti-tumor effects of ablative radiotherapy (RT). We used microarrays to study changes in gene expression patterns of inflammatory monocytes/macrophages sorted from the tumor microenvironment after ablative RT in a subcutenous model of pancreatic adenocarcinoma. From this, we identified 8 genes with an absolute fold change of expression equal to or greater than 2 with a false discovery rate equal to or less than 25 %. A pancreatic cancer tumor cell line derived from spontaneously arising tumors in KrasLSL-G12D/+, Trp53LSL-R172H/+, Pdx1-Cre (KPC) mice was subcutaneously implanted into 8 week old female C57BL/6 and allowed to grow for 14 days. After 14 days, 4 mice received 20 Gy of radiation, and 4 mice received a sham treatment. One day post treatment, tumors were harvested, and inflammatory monocytes/macrophages were isolated using flow sorting based on a surface expression phenotype of CD45+ CD11b+ Ly6Chi. From this cell population, total RNA was extracted for creation of cDNA and hybridization on Affymetrix microarrays. From the microarrays, a set of genes associated with radiation treatment of PDAC was identified.
2016-08-01 | E-GEOD-82276 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE39642: NanoString nCounter immune-related gene expression in blood sorted CD14+CD16- monocytes from sALS, fALS and HC subjects GSE39643: NanoString miRNA profiling of peripheral blood sorted CD14+CD16- monocytes from amyotrophic lateral sclerosis, multiple sclerosis and healthy control subjects Refer to individual Series
2012-07-25 | E-GEOD-39644 | biostudies-arrayexpress