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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 01, 2022 |
| Title |
Chemotherapy-induced complement signaling modulates immunosuppression and metastatic relapse in breast cancer [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Mortality from breast cancer is almost exclusively a result of tumor metastasis and resistance to therapy and therefore understanding the underlying mechanisms is an urgent challenge. Chemotherapy, routinely used to treat breast cancer, induces extensive tissue damage, eliciting an inflammatory response that may hinder efficacy and promote metastatic relapse. Here we show that systemic treatment with chemotherapy following resection of a triple-negative breast tumor induced the expression of complement factors in lung fibroblasts and modulated an immunosuppressive metastatic niche that supported lung metastasis. CAF-derived complement signaling mediated the recruitment of myeloid-derived suppressor cells (MDSCs) to the metastatic niche, thus promoting T cell dysfunction. Functionally, we show that pharmacological targeting of complement signaling in combination with chemotherapy alleviated immune dysregulation and attenuated lung metastasis. Our findings suggest that combining cytotoxic treatment with blockade of complement signaling in triple-negative breast cancer patients may attenuate the adverse effects of chemotherapy, thus offering a promising approach for clinical use.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for fibroblasts isolated from early stage metastatic lungs of mice treated with doxorubicin (Dox n=5) or saline as control (Pbs, n=4).
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| Contributor(s) |
Monteran L, Ershaid N, Doron H, Zait Y, Zait Y, Scharff Y, Ben-Yosef S, Avivi C, Barshack I |
| Citation(s) |
36184683 |
| Submission date |
Jul 15, 2022 |
| Last update date |
Oct 27, 2022 |
| Contact name |
Nour Ershaid |
| E-mail(s) |
nourersh@mail.tau.ac.il
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| Organization name |
Tel Aviv University
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| Street address |
Postal code 2373,
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| City |
Tel Aviv |
| State/province |
Israel |
| ZIP/Postal code |
1612301 |
| Country |
Israel |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| GSM6340241 |
Fibroblasts from early-met lungs of mice treated with vehicle (Pbs), biol rep 1 |
| GSM6340242 |
Fibroblasts from early-met lungs of mice treated with vehicle (Pbs), biol rep 2 |
| GSM6340243 |
Fibroblasts from early-met lungs of mice treated with vehicle (Pbs), biol rep 3 |
| GSM6340244 |
Fibroblasts from early-met lungs of mice treated with vehicle (Pbs), biol rep 4 |
| GSM6340245 |
Fibroblasts from early-met lungs of mice treated with doxorubicin (Dox), biol rep 1 |
| GSM6340246 |
Fibroblasts from early-met lungs of mice treated with doxorubicin (Dox), biol rep 2 |
| GSM6340247 |
Fibroblasts from early-met lungs of mice treated with doxorubicin (Dox), biol rep 3 |
| GSM6340248 |
Fibroblasts from early-met lungs of mice treated with doxorubicin (Dox), biol rep 4 |
| GSM6340249 |
Fibroblasts from early-met lungs of mice treated with doxorubicin (Dox), biol rep 5 |
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| Relations |
| BioProject |
PRJNA859133 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE208289_RAW.tar |
2.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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