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Series GSE233862 Query DataSets for GSE233862
Status Public on Jun 30, 2023
Title PTEN loss confers resistance to anti-PD-1 therapy in nonsmall cell lung cancer by increasing tumor infiltration of regulatory T cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Immunotherapy resistance in non-small cell lung cancer (NSCLC) may be mediated by an immunosuppressive microenvironment, which can be shaped by the mutational landscape of the tumor. Here, we observed genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression in >25% NSCLC patients, with higher frequency in lung squamous carcinomas (LUSCs). Patients with PTEN-low tumors had higher levels of PD-L1 and PD-L2 and showed worse progression-free survival when treated with immunotherapy. Development of a Ptennull LUSC mouse model revealed that tumors with PTEN loss were refractory to antiPD-1, highly metastatic and fibrotic, and secreted TGF-β/CXCL10 to promote conversion of CD4+ lymphocytes into regulatory T cells (Tregs). Human and mouse PTEN-low tumors were enriched in Tregs and expressed higher levels of immunosuppressive genes. Importantly, treatment of mice bearing Pten-null tumors with TLR agonists and anti-TGF-β antibody aimed to alter this immunosuppressive microenvironment led to tumor rejection and immunological memory in 100% of mice. These results demonstrate that lack of PTEN causes immunotherapy resistance in LUSC by establishing an immunosuppressive tumor microenvironment that can be reversed therapeutically.
Overall design We generated a PTEN mutant version of the murin lung squamous carcinoma UNSCC680 cells using CRISPR-Cas9 technology.
We performed RNAseq from in vitro cultured EVGFP control cells and PTEN mutant cells, at a single time-point.
Comparative gene-expression profiling of RNAseq between EVGFP (Control) and PTEN null cells.
Web link
Contributor(s) Calvo A, Exposito F
Citation(s) 37311042
Submission date May 31, 2023
Last update date Sep 29, 2023
Contact name Francisco Exposito
Organization name University of Navarra
Department Department of Pathology, Anatomy and Physiology, School of Medicine
Street address Irunlarrea SN, Research Building
City Pamplona
State/province Navarra
ZIP/Postal code 31008
Country Spain
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (3)
GSM7438264 Empty-vector GFP (EVGFP-Control)
GSM7438265 PTEN-null (PTEN-Mutant) [1]
GSM7438266 PTEN-null (PTEN-Mutant) [2]
BioProject PRJNA978248

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Supplementary file Size Download File type/resource
GSE233862_Raw_counts.txt.gz 1.4 Mb (ftp)(http) TXT
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Processed data are available on Series record

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