Transcriptomics,Genomics

Dataset Information

166

Response to programmed cell death-1 blockade in a murine melanoma syngeneic model requires costimulation, CD4 and CD8 T-cells


ABSTRACT: 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. Overall design: mRNA profiles of YUMM murine melanoma cell lines

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Jennifer Tsoi  

PROVIDER: GSE84264 | GEO | 2016-09-21

SECONDARY ACCESSION(S): PRJNA328490

REPOSITORIES: GEO

altmetric image

Publications

Response to Programmed Cell Death-1 Blockade in a Murine Melanoma Syngeneic Model Requires Costimulation, CD4, and CD8 T Cells.

Homet Moreno Blanca B   Zaretsky Jesse M JM   Garcia-Diaz Angel A   Tsoi Jennifer J   Parisi Giulia G   Robert Lidia L   Meeth Katrina K   Ndoye Abibatou A   Bosenberg Marcus M   Weeraratna Ashani T AT   Graeber Thomas G TG   Comin-Anduix Begoña B   Hu-Lieskovan Siwen S   Ribas Antoni A  

Cancer immunology research 20160902 10


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 mut  ...[more]

Similar Datasets

| GSE100808 | GEO
2016-02-10 | E-GEOD-77714 | ArrayExpress
2016-02-16 | E-GEOD-77924 | ArrayExpress
| GSE81698 | GEO
| GSE100807 | GEO
2020-04-16 | E-MTAB-7777 | ArrayExpress
| GSE84980 | GEO
| GSE110251 | GEO
| GSE121810 | GEO
| GSE96923 | GEO