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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 01, 2025 |
| Title |
Acquired resistance to immunotherapy by physical barriers with cancer cell–expressing collagens in non–small cell lung cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
sc-RNAseq in immunotherapy- sensitive+veh (n=2), sensitive+anti-PD1 (n=2), resistant+veh (n=2), resistant+anti-PD1 (n=2), resistant dKO+veh (n=2), resistant dKO+anti-PD1 (n=2), resistant + anti-PD1+veh (n=1) and resistant + anti-PD1+warfarin (n=1) mouse NSCLC groups.
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| Contributor(s) |
Wang M, Pan X, Liu Y, Chen C |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Mar 19, 2024 |
| Last update date |
May 26, 2025 |
| Contact name |
Xaingyu Pan |
| E-mail(s) |
pangxueyu233@outlook.com
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| Organization name |
Sichuan University
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| Department |
State Key Laboratory of Biotherapy, West China Hospital, Sihcuan University.
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| Lab |
Chen & Liu Lab
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| Street address |
No.17 Renming road section3
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| City |
Chengdu, Cihna |
| State/province |
Sichuan |
| ZIP/Postal code |
610041 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA1089539 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE261898_RAW.tar |
592.8 Mb |
(http)(custom) |
TAR (of TAR) |
| GSE261898_scRNA.NSCLC.all.rds.gz |
1.2 Gb |
(ftp)(http) |
RDS |
| GSE261898_scRNA.NSCLC.with.dKO.rds.gz |
1.3 Gb |
(ftp)(http) |
RDS |
| GSE261898_scRNA.Warfarin.Vehicle.rds.gz |
176.6 Mb |
(ftp)(http) |
RDS |
| GSE261898_scRNA.onlyT.Warfarin.Vehicle.rds.gz |
8.7 Mb |
(ftp)(http) |
RDS |
| GSE261898_scRNA.onlyT.with.dKO.rds.gz |
190.6 Mb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
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