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| Status |
Public on Apr 02, 2019 |
| Title |
Adaptive plasticity of IL10+ and IL35+ regulatory T cells cooperatively promote intratumoral T cell exhaustion |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Abstract: Regulatory T cells (Tregs) maintain host self-tolerance but are a major barrier to effective cancer immunotherapy. Tregs subvert beneficial anti-tumor immunity by modulating inhibitory receptor (IR) expression on tumor infiltrating lymphocytes (TILs); however, the underlying mediators and mechanisms remain elusive. Here we show that interleukin-10 (IL10) and interleukin-35 (IL35; a heterodimer of Ebi3 and IL12) are reciprocally expressed by Treg-subpopulations in the tumor microenvironment (TME) and cooperatively promote intratumoral T cell exhaustion. Treg-restricted deletion of either Il10/Ebi3 or dual deletion resulted in delayed tumor growth and significant reduction of transcriptomic exhaustion signature associated with reduced expression of B lymphocyte-induced maturation protein-1 (BLIMP1; Prdm1). While the two cytokines share the BLIMP1 axis to drive multi-IR expression; they differentially impact effector vs. memory fate, highlighting their overlapping and non-redundant regulation of anti-tumor immunity. Our results reveal previously unappreciated adaptive plasticity in inhibitory cytokine expression pattern by Tregs in TME for maximal immunosuppression.
Data purpose: to understand the segregated cytokine expression pattern and the preferential generation of single cytokine positive Treg subpopulations, we performed single cell RNASeq (scRNAseq) contrasting Tregs isolated from naïve, unchallenged LNs or day 14 B16 tumor from Foxp3Cre-YFP WT mice
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| Overall design |
LNs or day 14 B16 tumor from Foxp3Cre-YFP WT mice
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| Contributor(s) |
Sawant DV, Yano H |
| Citation(s) |
30936494 |
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| Submission date |
Feb 06, 2019 |
| Last update date |
Apr 10, 2019 |
| Contact name |
Wei Chen |
| E-mail(s) |
wei.chen@chp.edu
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| Organization name |
Children’s Hospital of Pittsburgh of UPMC
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| Department |
Division of Pulmonary Medicine, Allergy and Immunology, Department of Pediatrics
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| Street address |
4401 Penn Ave., Rangos Research Building, Room 9125
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| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15224 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
| GSM3592713 |
scRNA data of unchallenged lymph node from Foxp3Cre-YFP mouse |
| GSM3592714 |
scRNA data of B16 tumor from Foxp3Cre-YFP mouse |
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| Relations |
| BioProject |
PRJNA521251 |
| SRA |
SRP184268 |
