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| Status |
Public on Mar 03, 2020 |
| Title |
High-dimensional single cell analysis reveals an effector Treg molecular program that correlates with lung cancer progression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Anti-tumor immune responses are counteracted by CD4+ regulatory T (Treg) cells in the tumor micronenvironment, but the molecular mechanisms responsible for the enhanced suppressive activity of Tregs are poorly defined. High-dimensional single cell profiling of millions of single CD4+ and CD8+ T cells from 53 chemotherapy-na‹ve individuals with lung adenocarcinoma identified the transcription factor IRF4 as constitutively expressed by effector CD4+ Tregs present exclusively in tumors. These IRF4+, but not the quiescent IRF4_ÿTregs expressed a vast array of suppressive molecules, positively correlated with multiple inhibitory and exhausted subpopulations of T cells and were more abundant in rapidly progressing patients. Integration of transcriptomic data and whole genome binding sites of transcription factors further revealed that IRF4, either alone or in combination with its partner BATF, directly controlled a molecular program responsible for Treg hyperproliferation and suppressive functions that included CTLA-4, ICOS, TNFRSF9 (4-1BB) and IL1R2, previously shown to impact survival in lung cancer. Thus, interfering with the IRF4-dependent molecular program may represent a novel immunotherapeutic approach capable to block immunosuppression in the tumor microenvironment without inducing autoimmunity in peripheral tissues.ÿ
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| Overall design |
Transcriptional profiling of human tumor infiltrating Tregs. Gene expression profile of facs sorted Tregs (CD4+CD25+CD127-CCR8+ICOS+ and CD4+CD25+CD127-CCR8-ICOS-) from 5 surgically resected and cryopreserved human non small-cell lung cancer carcinomas.
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| Contributor(s) |
Alvisi G, Puccio S, Brummelman J, Paoluzzi Tomada E, Mazza E, Lugli E |
| Citation(s) |
32125291, 34552178 |
| Submission date |
Mar 25, 2019 |
| Last update date |
Oct 13, 2021 |
| Contact name |
Simone Puccio |
| E-mail(s) |
simone.puccio@humanitasresearch.it
|
| Organization name |
Humanitas Clinical and Research Center
|
| Lab |
Translational Immunology Lab
|
| Street address |
Via Alessandro Manzoni, 56
|
| City |
Rozzano |
| State/province |
Milan |
| ZIP/Postal code |
20089 |
| Country |
Italy |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA528966 |
| SRA |
SRP189378 |
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