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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 26, 2018 |
| Title |
Systematic immune reprogramming via PD-1 inhibition enhances early-stage lung cancer survival. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Success of immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC) has invigorated their use in neo-adjuvant setting for early-stage disease. However, the cellular and molecular mechanisms of the early immune responses to therapy remain poorly understood. Through an integrated analysis of early-stage NSCLC patients and a Kras-mutant mouse model, we show a prevalent programmed cell death 1/ programmed cell death 1 ligand 1 (PD-1/PD-L1) axis exemplified by increased intratumoral PD-1+ T cells and PD-L1 expression. Notably, tumor progression was associated with spatiotemporal modulation of the immune microenvironment. Importantly, PD-1 inhibition controlled tumor growth, improved overall survival, and reprogrammed tumor-associated lymphoid and myeloid cells. Depletion of T lymphocyte subsets demonstrated synergistic effects of those populations on PD-1 inhibition of tumor growth. Transcriptome analyses revealed T cell subset-specific alterations corresponding to degree of response to the treatment. These results provide insights into temporal evolution of the phenotypic effects of PD-1/PD-L1 activation and inhibition, and motivate targeting this axis early in lung cancer progression.
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| Overall design |
CD4 and CD8 lung tumor infiltrating lymphocytes were sorted into RLT lysis buffer from IgG antibody or anti-PD1 antibody treated C57Bl/6 mice at day 14, 17 or 24 for mRNA-Sequencing.
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| Contributor(s) |
Mittal V, Markowitz G |
| Citation(s) |
29997286, 37790365 |
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| Submission date |
May 10, 2018 |
| Last update date |
Oct 19, 2023 |
| Contact name |
Olivier Elemento |
| E-mail(s) |
ole2001@med.cornell.edu
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| Organization name |
Weill Cornell Medicine
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| Department |
Biochemistry
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| Street address |
1305 York Ave
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (62)
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| Relations |
| BioProject |
PRJNA470891 |
| SRA |
SRP145321 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE114300_RAW.tar |
7.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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