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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 05, 2024 |
| Title |
Interferon-stimulated neutrophils identified in preclinical models may serve as a potential biomarker for immunotherapy response in human |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Despite the remarkable success of immunotherapy, only ~20-30% of cancer patients display an extended durable response. Pre-existing biomarkers for immunotherapy outcome are significantly limited in their predictive power. While mice are the most widely used and cost-effective model to study human disease, translating preclinical biomarkers into clinical practice faces significant obstacles – in part due to the lack of diverse or appropriate models. Here, to improve translatability and identify novel biomarkers, we showcase an approach encompassing several pre-clinical models - each capturing one possible mechanistic aspect of immunotherapy response, such as tumor- and host-dependency, in order to reflect the variability seen in human cancers. Using this approach, we identify interferon-stimulated, Ly6Ehi neutrophils as a pre-treatment, blood-borne biomarker for anti-PD1 response in mice. We subsequently validate this result in cohorts of immunotherapy-treated non-small cell lung cancer (NSCLC) and melanoma patients, where the abundance of Ly6Ehi neutrophils predicts anti-PD1 response and further validated these results using available datasets for other cancers. Moreover, we demonstrate that these cells sensitize otherwise resistant tumors to anti-PD1 therapy, in part by directly activating cytotoxic T cells and contributing to tumor cell killing, while operate upstream of T cells in the immunotherapy response. Collectively, our study identifies a new and functionally active biomarker to predict immunotherapy outcome with potential clinical relevance.
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| Overall design |
GR1+ myeloid cells were isolated from non-responding or responding 4T1, breast carcinoma murine tumors (5 mice pooled per sample) using magnetic beads and analyzed using scRNAseq.
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| Contributor(s) |
Cooper TJ, Shaked Y |
| Citation(s) |
38181798 |
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| Submission date |
Mar 08, 2023 |
| Last update date |
Feb 26, 2024 |
| Contact name |
Timothy Jon Cooper |
| E-mail(s) |
timcooper@technion.ac.il
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| Organization name |
Technion – Israel Institute of Technology
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| Street address |
1 Efron St.
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| City |
Haifa |
| ZIP/Postal code |
3525422 |
| Country |
Israel |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA942320 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE226962_RAW.tar |
129.2 Mb |
(http)(custom) |
TAR (of LOOM, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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