Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1077945 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28006366_1.fastq.gz | Fastqsanger.gz | |||
| SRR28006366_2.fastq.gz | Fastqsanger.gz | |||
| SRR28006367_1.fastq.gz | Fastqsanger.gz | |||
| SRR28006367_2.fastq.gz | Fastqsanger.gz | |||
| SRR28006368_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Tumor-associated macrophages (TAMs) are a crucial factor in reprogramming the tumor microenvironment following radiotherapy. The mechanisms underlying this process remain to be elucidated. We used single cell RNA sequencing (scRNA-seq) to investigate the effects of hypofractionated radiotherapy on macrophages dynamics in a subcutaneous Lewis lung carcinoma (LLC) murine model.
2024-04-03 | GSE256051 | 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:BackgroundTumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated.MethodsSubcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining.ResultsTranscriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control.ConclusionsHypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.
| S-EPMC10964592 | biostudies-literature
Project description:Purpose: To study the alteration of whole transcriptome of Lewis lung carcinoma (LLC) cells after the decreasing of malignant properties of tumor by treatment of tumor-bearing mice with RNase A. Methods: Whole transcriptome profile of Lewis lung carcinoma before and after RNase A treatment were generated by deep sequencing using SOLiD 5.5. The sequence reads were mapped by Bioscope 1.3 software, differential expression was evaluated by Cufflinks v.2.0.1 package. Results: Difference in expression was found for 966 genes. Conclusions: Our study represents the first detailed analysis of alteration of transcriptome of Lewis lung carcinoma after the decrease of malignant prtoperties of the tumor (proliferation and invasion) by RNase A.
2014-12-03 | GSE63758 | GEO
Project description:Purpose: To study the alteration of whole transcriptome of Lewis lung carcinoma (LLC) cells after the decreasing of malignant properties of tumor by treatment of tumor-bearing mice with RNase A. Methods: Whole transcriptome profile of Lewis lung carcinoma before and after RNase A treatment were generated by deep sequencing using SOLiD 5.5. The sequence reads were mapped by Bioscope 1.3 software, differential expression was evaluated by Cufflinks v.2.0.1 package. Results: Difference in expression was found for 966 genes. Conclusions: Our study represents the first detailed analysis of alteration of transcriptome of Lewis lung carcinoma after the decrease of malignant prtoperties of the tumor (proliferation and invasion) by RNase A. Whole transcriptome profile of Lewis lung carcinoma before and after RNase A treatment were generated by deep sequencing using SOLiD 5.5.
2014-12-03 | E-GEOD-63758 | biostudies-arrayexpress
Project description:Radiotherapy is one of the most common therapies for cancer. Approximately half of all cancer patients will receive radiotherapy at some point during treatment. Consequences of IR treatment are dose dependent and different sensitivity to IR of various types of cells is well established. To reduce the damage of IR to most sensitive cells of normal (noncancerous) tissue radiotherapy is administered as fractionated dose treatment applying radiation in ~2 Gy fractions every 24 hours, 5 times per week. However, during the therapy intrinsic and acquired tumor radioresistance may result in treatment failures. Comprehensive mechanisms of the resistance to irradiation as well as mechanisms of cellular response to fractionated dose IR remain unclear. Therefore, in the present study we evaluated global gene expression changes in murine Lewis lung carcinoma LLC1 cells following X-ray irradiation of single 2 Gy or 10 Gy and 2 Gy x 5 fractionated doses. Total RNA was harvested from mouse Lewis lung carcinoma cells 4h after treatment of single (2 Gy or 10 Gy) or fractionated (5x2 Gy) ionizing radiation dose.
2016-07-07 | E-GEOD-84108 | biostudies-arrayexpress
Project description:Radiotherapy is one of the most common therapies for cancer. Approximately half of all cancer patients will receive radiotherapy at some point during treatment. Consequences of IR treatment are dose dependent and different sensitivity to IR of various types of cells is well established. To reduce the damage of IR to most sensitive cells of normal (noncancerous) tissue radiotherapy is administered as fractionated dose treatment applying radiation in ~2 Gy fractions every 24 hours, 5 times per week. However, during the therapy intrinsic and acquired tumor radioresistance may result in treatment failures. Comprehensive mechanisms of the resistance to irradiation as well as mechanisms of cellular response to fractionated dose IR remain unclear. Different gene expression patterns may be partially influenced by short ~22 nt non-coding RNA molecules called microRNAs (miRNAs) via translational regulation or RNA degradation mechanisms. Therefore, in the present study we evaluated global miRNA changes in murine Lewis lung carcinoma LLC1 cells following X-ray irradiation of single 2 Gy or 10 Gy and 2 Gy x 5 fractionated doses. Total RNA enriched in small noncoding RNAs was isolated from mouse Lewis lung carcinoma cells 4h after treatment of single (2 Gy or 10 Gy) or fractionated (5x2 Gy) ionizing radiation dose.
2016-07-07 | E-GEOD-84109 | biostudies-arrayexpress
Project description:Transcriptional profiling of tumor-infiltrating antigen-presenting myeloid subsets and CD8 T cells in mice bearing MC38-OVA tumors treated with or without radiotherapy, αSIRPα, and/or αPD-1 treatment
2022-04-19 | GSE197767 | GEO
Project description:Radiotherapy is standard of care for inoperable non-small cell lung cancers (NSCLC) but adenocarcinoma NSCLC respond more poorly than squamous cell NSCLC. Transforming growth factor β (TGFβ) activity is induced by radiation and plays a recently recognized role in the DNA damage response. Here we show in murine lung tumor model that radiation activates TGFβ acutely and persistently and that TGFβ neutralizing antibody, 1D11, systemic treatment increased tumor control following either fractionated or single high dose radiation regimes. TGFβ dependent genes in the irradiated tumor indicated crosstalk between innate and adaptive immunity but therapeutic benefit of 1D11 in irradiated tumors in immunocompromised mice suggested that innate immune cells are more influential than the adaptive immune response. Irradiated tumors in which TGFβ was blocked were highly hypoxic, exhibit pronounced microvascular damage and promoted neither cancer-associated fibroblasts nor recruit bone marrow derived cells (BMDC). Tumor educated immature BMDC were significant sources of TGFβ and inhibiting BMDC recruitment achieved tumor growth control in response to RT comparable to TGFβ inhibition. Thus, radiation-induced TGFβ both compromises tumor control by RT and promotes reestablishment of the tumor microenvironment. Concordant with the critical role of TGFβ activity in RT, radiation resistant NSCLC adenocarcinomas exhibit higher TGFβ activity compared to squamous cell NSCLC, which suggests a rationale for using TGFβ inhibition to augment radiotherapy. Lewis lung cancer (LLC) model were established in 6 to 8 week-old C57BL/6 female mice by subcutaneous injection. When tumors were 60-80 mm3, Mice were randomized to achieve comparable mean tumor size for each treatment group as indicated below. Tumor growth were monitored and tumors were collected and characterized by gene expression profiling and immunostaining.
2015-12-15 | E-GEOD-73095 | biostudies-arrayexpress