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Series GSE125383 Query DataSets for GSE125383
Status Public on Feb 12, 2019
Title Macrophage phenotype in anti-PD-L1 treated MC38 tumors
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Checkpoint inhibitors like anti-PD1/PD-L1 have demonstrated significant therapeutic efficacy in a subset of patients partly through reinvigoration of CD8 T cells. However, their impact on myeloid cells remains largely unknown. Here we report that anti-PD-L1 treatment favorably impacts the phenotype and function of tumor macrophages by polarizing the macrophage compartment towards a more pro-inflammatory phenotype. This phenotype was characterized by a decrease in Arginase-I (ARG1) expression and an increase in iNOS, MHCII, and CD40 expression. Whole-transcriptome profiling further confirmed extensive polarization of both tumor monocytes and macrophages from a suppressive to a pro-inflammatory, immuno-stimulatory phenotype. This polarization was driven mainly through IFNγ and was associated with enhanced T cell activity. Transfer of monocytes into anti-PD-L1-treated tumor-bearing mice led to macrophage differentiation into a more pro-inflammatory phenotype, with an increase in CD8 T cells expressing granzyme B and an increase in the CD8/Treg ratio compared to control-treated mice. While in responsive tumor models anti-PD-L1 treatment remodeled the macrophage compartment with beneficial effects on T cells, both macrophage reprogramming and depletion were needed to maximize anti-PD-L1 responses in a tumor immune contexture with high macrophage burden. Our results demonstrate that anti-PD-L1 treatment can favorably remodel the macrophage compartment in responsive tumor models towards a more pro-inflammatory phenotype, mainly through increased IFNγ levels. They also suggest that directly targeting these cells with reprogramming and depleting agents may further augment the breadth and depth of response to anti-PD-L1 treatment in less responsive or more macrophage-dense tumor microenvironments.

The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech.
The ID of this project in Genentech's ExpressionPlot database is NGS1772.
Overall design RNA isolated from sorted macrophages and monocytes from control or anti-PD-L1 treated MC38 tumors 7 days after treatment initiation.
Contributor(s) Nickles D, Cubas R
Citation(s) 30679180
Submission date Jan 20, 2019
Last update date Mar 21, 2019
Contact name Dorothee Nickles
Organization name Genentech
Street address 1 DNA Way
City South San Francisco
State/province CA
ZIP/Postal code 94080
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (20)
GSM3573131 SAM24342237 Macrophage aPDL1
GSM3573132 SAM24342230 Monocyte ctrl
GSM3573133 SAM24342225 Macrophage ctrl
BioProject PRJNA516065
SRA SRP180887

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE125383_RAW.tar 5.8 Mb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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