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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 02, 2019 |
| Title |
Adaptive plasticity of IL10 + and IL35 + regulatory T cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Regulatory T cells (T regs) maintain host self-tolerance but are a major barrier to effective cancer immunotherapy. T regs 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; Ebi3/IL12α heterodimer) are divergently expressed by T reg subpopulations in the tumor microenvironment (TME) and cooperatively promote intratumoral T cell exhaustion. T reg -restricted deletion of Il10 and/or Ebi3 resulted in delayed tumor growth, loss of multi-IR expression, and reduced intratumoral CD8 + T cell exhaustion signature. While Il10 or Ebi3 loss was associated with reduced expression of B lymphocyte-induced maturation protein-1 (BLIMP1; Prdm1), IL10 and IL35 differentially impacted effector versus memory T cell fates, respectively, highlighting their differential, partially overlapping but non-redundant regulation of anti-tumor immunity. Our results reveal previously unappreciated cooperative roles for IL10 and IL35, produced by limits effective anti-tumor immunity
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| Overall design |
TIL CD8 cells from Treg specific IL10, IL35 and double knockouts, sorted into populations based on exhaustion markers. TIL Tregs sorted based on IL10 and IL35 expression.
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| Contributor(s) |
Chikina M |
| Citation(s) |
30936494 |
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| Submission date |
Mar 01, 2019 |
| Last update date |
Apr 10, 2019 |
| Contact name |
Maria Chikina |
| E-mail(s) |
mchikina@gmail.com
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| Organization name |
University of Pittsburgh
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| Street address |
3501 5th ave
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| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15260 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (90)
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| Relations |
| BioProject |
PRJNA525180 |
| SRA |
SRP187323 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE127735_CD8NormFiltered.txt.gz |
4.7 Mb |
(ftp)(http) |
TXT |
| GSE127735_CombinedRawCounts.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
| GSE127735_TregNormFiltered.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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