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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 21, 2016 |
| Title |
Response to programmed cell death-1 blockade in a murine melanoma syngeneic model requires costimulation, CD4 and CD8 T-cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The programmed cell death protein 1 (PD-1) limits effector T-cell functions in peripheral tissues and its inhibition leads to clinical benefit in different cancers. To better understand how PD-1 blockade therapy modulates the tumor-host interactions, we evaluated three syngeneic murine tumor models, the BRAFV600E-driven YUMM1.1 and YUMM2.1 melanomas, and the carcinogen-induced murine colon adenocarcinoma MC38. The YUMM cell lines were established from mice with melanocyte-specific BRAFV600E mutation and PTEN loss (BRAFV600E/PTEN-/-). Administration of anti-PD-1 or anti-PD-L1 antibody therapy had strong antitumor activity against MC38 and YUMM2.1, but not YUMM1.1. There was no difference in PD-L1 expression between the three models at baseline or upon interferon stimulation. While mutational load was high in MC38, it was lower in both YUMM models. In YUMM2.1, the antitumor activity of PD-1 blockade had a critical requirement for both CD4 and CD8 T-cells, as well as CD28 and CD80/86 co-stimulation, with an increase in CD11c+CD11b+MHC-IIhigh dendritic cells and tumor associated macrophages in the tumors after PD-1 blockade. Compared to YUMM1.1, YUMM2.1 exhibited a more inflammatory profile by RNA sequencing analysis, with an increase in chemokine-trafficking gene expression levels related to immune cell recruitment and T-cell priming. In conclusion, response to PD-1 blockade therapy in tumor models requires CD4 and CD8 T cells, and co-stimulation mediated by dendritic cells and macrophages.
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| Overall design |
mRNA profiles of YUMM murine melanoma cell lines
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| Contributor(s) |
Homet Moreno B, Zaretsky J, Garcia-Diaz A, Tsoi J, Parisi G, Robert L, Meeth K, Ndoye A, Bosenberg M, Weeraratna AT, Graeber TG, Comin-Anduix B, Hu-Lieskovan S, Ribas A |
| Citation(s) |
27589875 |
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| Submission date |
Jul 11, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Jennifer Tsoi |
| E-mail(s) |
[email protected]
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| Organization name |
UCLA
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| Department |
University of California, Los Angeles
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| Lab |
Thomas Graeber
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| Street address |
570 Westwood Blvd, CNSI 4338
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA328490 |
| SRA |
SRP078263 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE84264_YUMM_RNASeq_normalized_FPKM.xlsx.gz |
1007.3 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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