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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 08, 2024 |
| Title |
IFN𝛾-induced Immunosuppression in Lung Carcinoma is Mediated by an Environmental Chemical Receptor (AhR) through PD-L1 and IDO Control (cm167 bulk RNA) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
While immunotherapy has shown efficacy in non-small cell lung cancer (NSCLC) patients, many respond only partially or not at all. One limitation in improving outcomes is the lack of a complete understanding of factors regulating immune checkpoint targets. Here, we sought to address a possible link between an environmental chemical receptor implicated in NSCLC and immune regulation, the aryl hydrocarbon receptor (AhR), and a known but counterintuitive mediator of immunosuppression, IFN𝛾, in regulation of two immune checkpoints, PD-L1 and the IDO1, in lung adenocarcinoma (LUAD). To this end we used AhR, PD-L1, and IFN𝛾R gene-edited LUAD cell lines, a syngeneic LUAD mouse model, bulk- and single cell-RNA sequencing of LUADs and tumor-infiltrating leukocytes, and existing human transcriptomic databases. The data demonstrate that: 1) the AhR regulates both PD-L1 and IDO1 in murine and human LUAD cells, 2) AhR-driven IDO1 results in production of Kyn which likely mediates an AhR→IDO1→Kyn→AhR amplification loop, 3) the previously characterized induction by IFN𝛾of PD-L1 and IDO is mediated by the AhR, 4) transplantation of LUAD cells in which the AhR is deleted results in long-term tumor immunity in approximately half of the mice; slow growing tumors in the other half exhibit significantly higher densities of CD4+ and CD8+ T cells expressing immunocompetence markers, and 5) deletion of either IFN𝛾R1 or PD-L1 does not provide the same level of immune protection as AhR deletion. The data definitively link IFN𝛾- mediated immunosuppression to the AhR and support the targeting of the AhR in the context of LUAD.
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| Overall design |
The experiment is comprised of 6 samples, profiling RNA extracted from mouse CMT 167 (C57 mouse tumor; referred to herein as CMT) cell lines. Each cell line was either unmodified (naive, or "wild-type"), subjected to CRISPR with a non-targeting control sgRNA, or subjected to CRISPR with an sgRNA designed to knock out the aryl hydrocarbon receptor (Ahr) gene. Each experimental group was represented in triplicate.
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| Contributor(s) |
Snyder M, Wang Z, Lara B, Fimbres J, Mohammed MK, Monti S, Sherr DH |
| Citation(s) |
39185148 |
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| Submission date |
Aug 30, 2023 |
| Last update date |
Sep 27, 2024 |
| Contact name |
David H Sherr |
| E-mail(s) |
dsherr@bu.edu
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| Phone |
+1 6173125043
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| Organization name |
Boston University
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| Department |
Environmental Health
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| Street address |
72 East Concord St
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
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| Platforms (1) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE241980 |
IFN𝛾-induced Immunosuppression in Lung Carcinoma is Mediated by an Environmental Chemical Receptor (AhR) through PD-L1 and IDO Control |
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| Relations |
| BioProject |
PRJNA1010848 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE241978_2020-07-21_Sherr_analysis_CMT_KO_vs_Cas9Ctrl.xlsx |
14.4 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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