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Series GSE145905 Query DataSets for GSE145905
Status Public on May 19, 2020
Title PD-L1 Engagement on T cells Promotes Self-tolerance and Suppression of Neighboring Macrophages and Effector T cells in Cancer
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary PD-1 ligation delimits immunogenic responses in T cells. However, the consequences of PD-L1 ligation in T cells are uncertain. We found that T cell expression of PD-L1 in cancer was regulated by tumor-antigen, microbial signals, and sterile inflammatory cues. PD-L1+ T cells exerted tumor-promoting tolerance via three distinct mechanisms: (i) Binding of PD-L1 induced STAT3-dependent back-signaling in CD4+ T cells preventing activation, reducing Th1-polarization, and directing Th17-differentiation. PD-L1 signaling also induced an anergic Tbet-IFNg- phenotype in CD8+ T cells and was equally suppressive compared to PD-1 signaling. (ii) PD-L1+ T cells restrained effector T cells via the canonical PD-L1-PD-1 axis and were sufficient to accelerate tumorigenesis even in the absence of endogenous PD-L1. (iii) PD-L1+ T cells engaged PD-1+ macrophages inducing an alternative M2-like program, which had crippling effects on adaptive anti-tumor immunity. Collectively, we demonstrate that PD-L1+ T cells have diverse tolerogenic effects on tumor immunity.
 
Overall design For RNA-Seq experiments, mouse PDL1 knockout and wild-type T cells were stimulated in vitro using anti-CD3 and anti-CD28. Alternatively, CD45+ leukocytes were FACS-sorted from mouse pancreatic tumors 3 weeks after orthotopic implantation.
 
Contributor(s) Aykut B, Khodadadi-Jamayran A, Miller G
Citation(s) 32152508
Submission date Feb 25, 2020
Last update date May 19, 2020
Contact name Alireza Khodadadi-Jamayran
Organization name New York University, NYU Langone Medical Center
Department Division of Advanced Research Technologies (DART)
Lab Applied Bioinformatics Laboratories (ABL)
Street address 550 1st Ave, MSB 304
City New York City
State/province NY
ZIP/Postal code 10016
Country USA
 
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (17)
GSM4339159 Control_1 (RNA-seq)
GSM4339160 Control_2 (RNA-seq)
GSM4339161 Control_3 (RNA-seq)
Relations
BioProject PRJNA608709
SRA SRP250701

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Supplementary file Size Download File type/resource
GSE145905_RAW.tar 587.8 Mb (http)(custom) TAR (of BW, MTX, TSV, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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