Acquired resistance to immunotherapy by physical barriers with cancer cell–expressing collagens in non–small cell lung cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1089513 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28385666_1.fastq.gz | Fastqsanger.gz | |||
| SRR28385666_2.fastq.gz | Fastqsanger.gz | |||
| SRR28385667_1.fastq.gz | Fastqsanger.gz | |||
| SRR28385667_2.fastq.gz | Fastqsanger.gz | |||
| SRR28385668_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 38 |
Similar Datasets
Project description:Drug resistance is the principal challenge of cancer therapies, including recently developed immunotherapy. More and more popular use of immunotherapy, especially treatments with immune checkpoint inhibitors (ICIs), witnesses explosively increasing cases of both primary and acquired immunotherapy resistance. While primary resistance has been extensively studied, mechanisms underlying acquired resistance of immunotherapy are less understood. Here we reported that tumor cells could develop acquired resistance to ICI treatment through self-built collagen-containing physical barriers in non-small cell lung cancer (NSCLC). We found that tumor cells expressed high levels of multiple collagen genes, including COL3A1 and COL6A1, and were fully covered with collagen fibers. COL3A1 formed a castle-like structure of a cluster of tumor cells and prevented the infiltration of T cells, while COL6A1 seemed to be an armor-like structure of each tumor cell and protected them from attack by cytotoxic T cells. Genetic or pharmaceutic disruption of these collagens, by warfarin, a commonly used medicine, significantly reversed the acquired resistance. Thus, our data reveal an unprecedented tumor cell-intrinsic mechanism, mediated by collagen-containing physical barriers, of acquired immunotherapy resistance, which immediately suggests a treatment option for patients.
2025-05-22 | GSE261597 | GEO
Project description:Drug resistance is the principal challenge of cancer therapies, including recently developed immunotherapy. More and more popular use of immunotherapy, especially treatments with immune checkpoint inhibitors (ICIs), witnesses explosively increasing cases of both primary and acquired immunotherapy resistance. While primary resistance has been extensively studied, mechanisms underlying acquired resistance of immunotherapy are less understood. Here we reported that tumor cells could develop acquired resistance to ICI treatment through self-built collagen-containing physical barriers in non-small cell lung cancer (NSCLC). We found that tumor cells expressed high levels of multiple collagen genes, including COL3A1 and COL6A1, and were fully covered with collagen fibers. COL3A1 formed a castle-like structure of a cluster of tumor cells and prevented the infiltration of T cells, while COL6A1 seemed to be an armor-like structure of each tumor cell and protected them from attack by cytotoxic T cells. Genetic or pharmaceutic disruption of these collagens, by warfarin, a commonly used medicine, significantly reversed the acquired resistance. Thus, our data reveal an unprecedented tumor cell-intrinsic mechanism, mediated by collagen-containing physical barriers, of acquired immunotherapy resistance, which immediately suggests a treatment option for patients.
2025-02-01 | GSE261898 | GEO
Project description:Drug resistance is the principal challenge of cancer therapies, including recently developed immunotherapy. More and more popular use of immunotherapy, especially treatments with immune checkpoint inhibitors (ICIs), witnesses explosively increasing cases of both primary and acquired immunotherapy resistance. While primary resistance has been extensively studied, mechanisms underlying acquired resistance of immunotherapy are less understood. Here we reported that tumor cells could develop acquired resistance to ICI treatment through self-built collagen-containing physical barriers in non-small cell lung cancer (NSCLC). We found that tumor cells expressed high levels of multiple collagen genes, including COL3A1 and COL6A1, and were fully covered with collagen fibers. COL3A1 formed a castle-like structure of a cluster of tumor cells and prevented the infiltration of T cells, while COL6A1 seemed to be an armor-like structure of each tumor cell and protected them from attack by cytotoxic T cells. Genetic or pharmaceutic disruption of these collagens, by warfarin, a commonly used medicine, significantly reversed the acquired resistance. Thus, our data reveal an unprecedented tumor cell-intrinsic mechanism, mediated by collagen-containing physical barriers, of acquired immunotherapy resistance, which immediately suggests a treatment option for patients.
2025-02-01 | GSE261889 | GEO
Project description:Acquired resistance to immunotherapy by physical barriers with cancer cell–expressing collagens in non–small cell lung cancer
| PRJNA1089539 | ENA
Project description:Acquired resistance to immunotherapy by physical barriers with cancer cell–expressing collagens in non–small cell lung cancer
| PRJNA1088081 | ENA
Project description:Eukaryotic genomes are compacted into loops and topologically associating domains (TADs), which contribute to transcription, recombination and genomic stability. Cohesin extrudes DNA into loops that are thought to lengthen until it encounters CTCF boundaries. Little is known whether loop extrusion is impeded by macromolecular machines. We demonstrate that the replicative helicase MCM is a barrier that restricts loops and TADs in G1 phase. Single-nucleus Hi-C of one-cell embryos revealed that MCM loading reduces CTCF-anchored loops and increases TAD boundary insulation, suggesting loop extrusion is impeded before reaching CTCF. Single-molecule imaging provides evidence that MCM are physical barriers that constrain cohesin translocation in vitro. Simulations are consistent with MCM as abundant, random barriers with low permeability. We conclude that distinct loop extrusion barriers contribute to shaping 3D genomes.
2022-03-07 | GSE155971 | GEO
Project description:Eukaryotic genomes are compacted into loops and topologically associating domains (TADs), which contribute to transcription, recombination and genomic stability. Cohesin extrudes DNA into loops that are thought to lengthen until CTCF boundaries are encountered. Little is known about whether loop extrusion is impeded by DNA-bound macromolecular machines. We demonstrate that the replicative helicase MCM is a barrier that restricts loop extrusion in G1 phase. Single-nucleus Hi-C of one-cell embryos revealed that MCM loading reduces CTCF-anchored loops and decreases TAD boundary insulation, suggesting loop extrusion is impeded before reaching CTCF. Single-molecule imaging shows that MCMs are physical barriers that constrain cohesin translocation in vitro. Simulations are consistent with MCMs as abundant, random barriers. We conclude that distinct loop extrusion barriers contribute to shaping 3D genomes.
2022-03-08 | GSE196300 | GEO
Project description:Dysfunctional brain barriers contribute to the pathophysiology of chronic CNS diseases, but few non-viral technologies are established that effectively target these interfaces. In this work, we developed a lipid-siRNA conjugate that modulate gene expression in brain barriers such as the blood-brain-barrier (BBB), which describes the restrictive properties of brain microvascular endothelial cells (BMEC), as well as the blood-CSF-barrier (BCSFB) formed by the choroid plexus. We showed robust delivery and knockdown in brain endothelial cells and the choroid plexus. In this experiment, we used single cell RNA sequencing to determine which CNS cell types exhibit siRNA-mediated gene silencing. To that end, we administered a 20 mg/kg intravenous dose of our lipid siRNA conjugate targeting Ppib or a non-targeting control. Brains were dissociated into single cells and processed for sequencing using PIPseq workflow. We found that gene silencing was specific to the brain barriers; we only detected knockdown in brain endothelial and choroid plexus epithelial cells.
2025-04-02 | E-MTAB-14840 | biostudies-arrayexpress
Project description:Eukaryotic genomes are compacted into loops and topologically associating domains (TADs), which contribute to transcription, recombination and genomic stability. Cohesin extrudes DNA into loops that are thought to lengthen until CTCF boundaries are encountered. Little is known about whether loop extrusion is impeded by DNA-bound machines. Here we show that the minichromosome maintenance (MCM) complex is a barrier that restricts loop extrusion in G1 phase. Single-nucleus Hi-C of mouse zygotes revealed that MCM loading reduces CTCF-anchored loops and decreases TAD boundary insulation, suggesting loop extrusion is impeded before reaching CTCF. This effect extends to HCT116 cells, where MCMs affect the number of CTCF-anchored loops and gene expression. Simulations suggest that MCMs are abundant, randomly positioned, partially permeable barriers. Single-molecule imaging shows that MCMs are physical barriers that frequently constrain cohesin translocation in vitro. Remarkably, chimaeric yeast MCMs harbouring a cohesin-interaction motif from human MCM3 induce cohesin pausing, suggesting that MCMs are “active” barriers with binding sites. These findings raise the possibility that cohesin can arrive by loop extrusion at MCMs, which determine the genomic sites at which sister chromatid cohesion is established. Based on in vivo, in silico and in vitro data, we conclude that distinct loop extrusion barriers shape the 3D genome.
2022-03-08 | GSE196496 | GEO
Project description:Nucleosomes are barriers to transcription in vitro, however, their effects on RNA polymerase in vivo are unknown. Here we describe a simple and general strategy to comprehensively map the positions of elongating and arrested RNA Polymerase II (RNAPII) at nucleotide resolution. Our results suggest that nucleosomes present significant, context-specific barriers to RNAPII in vivo that can be tuned by the incorporation of H2A.Z. 8 sets of two replicates each of paired-end and 3 sets of two replicates each of single-end samples were sequenced and analyzed.
2014-03-06 | E-GEOD-49106 | biostudies-arrayexpress