Tumor and immune remodeling following radiotherapy in human renal cell carcinoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA835807 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19119613_1.fastq.gz | Fastqsanger.gz | |||
| SRR19119613_2.fastq.gz | Fastqsanger.gz | |||
| SRR19119614_1.fastq.gz | Fastqsanger.gz | |||
| SRR19119614_2.fastq.gz | Fastqsanger.gz | |||
| SRR19119615_1.fastq.gz | Fastqsanger.gz |
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Project description:We performed single-cell analysis of renal cell carcinoma tumors from patients treated with or without radiotherapy to address how treatment shapes the immune compartment and interactions with cancer cells. We identified increased transition from stem-like T cell populations to effector and exhausted T cells in irradiated tumors.
2022-12-31 | GSE202374 | GEO
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:Mathematical modeling of regulatory T cell effects on renal cell carcinoma treatment
Lisette dePillis 1, , Trevor Caldwell 2, , Elizabeth Sarapata 2, and Heather Williams 2,
1.
Department of Mathematics, Harvey Mudd College, Claremont, CA 91711
2.
Harvey Mudd College, Claremont, CA 91711, United States, United States, United States
Abstract
We present a mathematical model to study the effects of the regulatory T cells (Treg) on Renal Cell Carcinoma (RCC) treatment with sunitinib. The drug sunitinib inhibits the natural self-regulation of the immune system, allowing the effector components of the immune system to function for longer periods of time. This mathematical model builds upon our non-linear ODE model by de Pillis et al. (2009) [13] to incorporate sunitinib treatment, regulatory T cell dynamics, and RCC-specific parameters. The model also elucidates the roles of certain RCC-specific parameters in determining key differences between in silico patients whose immune profiles allowed them to respond well to sunitinib treatment, and those whose profiles did not.
Simulations from our model are able to produce results that reflect clinical outcomes to sunitinib treatment such as: (1) sunitinib treatments following standard protocols led to improved tumor control (over no treatment) in about 40% of patients; (2) sunitinib treatments at double the standard dose led to a greater response rate in about 15% the patient population; (3) simulations of patient response indicated improved responses to sunitinib treatment when the patient's immune strength scaling and the immune system strength coefficients parameters were low, allowing for a slightly stronger natural immune response.
Keywords: Renal cell carcinoma, mathematical modeling., sunitinib, immune system, regulatory T cells.
2024-09-02 | BIOMD0000000908 | BioModels
Project description:Clear cell renal carcinoma (CCRC) accounts for >80% of all kidney cancers but what triggers the tumorigenesis in the kidney and metastases in the bones are still under debate. Our hypothesis is that remodeling of the genomic fabrics of certain functional pathways and their interplay beyond critical limits are key causes of CCRC. We profiled the transcriptomes of metastatic chest wall and of two primary cancerous sites of the renal medulla and compared them with that of non-cancerous kidney resection margins. Samples were collected from a 74 years old male with metastatic carcinoma, consistent with renal cell carcinoma, clear cell type, Fuhrman grade 3, who undergone total right kidney nephrectomy and resection of a chest wall mass. Transcriptomic analysis pointed the tumor region in the right kidney that led to the chest wall metastases. The tumor proved heterogeneous not only in the expression level but also in the expression control, coordination and interplay of pathways responsible for cellular processes and genetic and environmental information processing. The differently regulated pathways in the two sides of the tumor: CCRC, and HIF-1, Vegfa and mTor signaling indicate activation of distinct mechanisms. Four-conditions (CTR = control - non-cancerous kidney resection margins, PTA = primary tumor side A, PTB = primary tumor side B, MET = chest wall metastasis. Four biological replicates of each condition.
2015-08-24 | E-GEOD-72304 | biostudies-arrayexpress
Project description:BackgroundStudies evaluating peripheral patient samples show radiation can modulate immune responses, yet the biological changes in human tumors particularly at the cellular level remain largely unknown. Here, we address how radiation treatment shapes the immune compartment and interactions with cancer cells within renal cell carcinoma (RCC) patient tumors.MethodsTo identify how radiation shaped the immune compartment and potential immune interactions with tumor cells we evaluated RCC tumors from patients treated only with nephrectomy or with radiation followed by nephrectomy. Spectral flow cytometry using a 35-marker panel was performed on cell suspensions to evaluate protein expression within immune subsets. To reveal how radiation alters programming of immune populations and interactions with tumor cells, we examined transcriptional changes by single-cell RNA sequencing (scRNAseq).ResultsSpectral flow cytometry analysis revealed increased levels of early-activated as well as effector programmed cell death protein-1 (PD-1)+ CD8 T-cell subsets within irradiated tumors. Following quality control, scRNAseq of tumor samples from nephrectomy-only or radiation followed by nephrectomy-treated patients generated an atlas containing 34,626 total cells. Transcriptional analysis revealed increased transition from stem-like T-cell populations to effector T cells in irradiated tumors. Interferon (IFN) pathways, that are central to radiation-induced immunogenicity, were enriched in irradiated lymphoid, myeloid, and cancer cell populations. Focused cancer cell analysis showed enhanced antigen presentation and increased predicted TRAIL-mediated and IFN-mediated interactions between tumor cells and the same effector T-cell subsets increased by radiation. TRAIL and IFN pathways enriched in irradiated tumors were associated with survival in patients treated with immunotherapy.ConclusionsThese findings identify the source of IFN enrichment within irradiated RCC and reveal heightened levels of PD-1+ CD8+ T-cell subsets and increased probability of interactions with tumor cells following standalone radiation treatment. This study provides a window into the irradiated tumor-immune microenvironment of patients and rationale for treatment combinations.
| S-EPMC10124322 | biostudies-literature
Project description:Renal papillary cell carcinoma
| PRJNA749556 | ENA
Project description:Clear cell renal carcinoma (CCRC) accounts for >80% of all kidney cancers but what triggers the tumorigenesis in the kidney and metastases in the bones are still under debate. Our hypothesis is that remodeling of the genomic fabrics of certain functional pathways and their interplay beyond critical limits are key causes of CCRC. We profiled the transcriptomes of metastatic chest wall and of two primary cancerous sites of the renal medulla and compared them with that of non-cancerous kidney resection margins. Samples were collected from a 74 years old male with metastatic carcinoma, consistent with renal cell carcinoma, clear cell type, Fuhrman grade 3, who undergone total right kidney nephrectomy and resection of a chest wall mass. Transcriptomic analysis pointed the tumor region in the right kidney that led to the chest wall metastases. The tumor proved heterogeneous not only in the expression level but also in the expression control, coordination and interplay of pathways responsible for cellular processes and genetic and environmental information processing. The differently regulated pathways in the two sides of the tumor: CCRC, and HIF-1, Vegfa and mTor signaling indicate activation of distinct mechanisms.
2015-08-24 | GSE72304 | GEO
Project description:The proteome of clinical tissue samples diagnosed with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were evaluated analyzed along with the dataset identifier PXD022018 to establish a potential discriminative biomarker panel of proteins for these tumors subtypes.
2021-12-15 | PXD023296 | Pride
Project description:microRNA profiling in renal carcinoma
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Project description:To examine whether the local carbon ion radiotherapy affects the characteristics of the metastatic tumors, the expression profiles of the primary tumors and the lung metastases were studied in a mouse squamous cell carcinoma model by applying local radiotherapy with no irradiation (negative control), gamma-ray irradiation (reference beam), and carbon-ion irradiation. Keywords: mouse, squamous cell carcinoma, primary tumor, lung metastases, radiotherapy, carbon ion, gamma ray
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