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Senescence rewires microenvironment sensing to facilitate anti-tumor immunity (bulk RNA-Seq)

UID: 11061

Author(s): Chen, Hsuan-An*, Ho, Yu-jui*, Mezzadra, Riccardo*, Adrover, Jose M., Smolkin, Ryan*, Zhu, Changyu*, Luan, Wei*, Wuest, Alexandra*, Tian, Sha*, Li, Xiang*, Hendrickson, Ronald C.*, Egeblad, Mikala, Alonso-Curbelo, Direna*, Lowe, Scott W.* * MSK affiliated

Description
Summary from GEO:

"Cellular senescence involves a stable cell cycle arrest coupled to a secretory program that, in some instances, stimulates the immune clearance of senescent cells. Using an immune competent tumor model in which senescence triggers CD8 T cell-mediated tumor rejection, we show that senescence also remodels cell surface proteome to alter how they sense environmental factors, as exemplified by Type II interferon gamma (IFN-γ). Compared to proliferating cells, senescent cells upregulate IFN-γ receptor, become hypersensitized to microenvironmental IFN-γ, and more robustly induce antigen presenting machinery -effects also recapitulated in human tumor cells treated with senescence-inducing drugs. Disruption of the IFN-γ sensing by senescent cells blunts their immune-mediated clearance without disabling their characteristic secretory program or immune cell recruitment. Our results demonstrate that senescent cells have an enhanced ability to both send and receive environmental signals, and imply that each process is required for their effective immune surveillance."

Overall design from GEO:

"Transcriptomic characterization of in vitro proliferating (p53 suppressed) and senescent Nras mutant-p53 retorable (NSP) liver tumor cells:1) comparison between proliferating and senescent cells induced by different triggers (p53 restoration, trametinib+palbociclib); 2) identification of BRD4-dependent transcriptional programs by JQ1 treatment upon proliferating and senescent (p53-restored) cells; 3) characterization of the effect of IFNg on proliferating or senescent (p53-restored) cells. For in vivo bulk tumor RNA-seq, proliferating tumor (p53 suppressed) was harvested 7-10 day after randomization point and senescent-induced tumor (p53 restored) was harvested 12 days after p53 restoration, allowing similar size of tumor at harvest."
Subject of Study
Mus musculus
Subject(s)
CD8-Positive T-Lymphocytes
Cell Cycle Checkpoints
Cellular Senescence
RNA-Seq
Tumor Suppressor Protein p53
Access via GEO


Accession #: GSE203140

Access via BioProject


Accession #: PRJNA838824

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus and BioProject databases provides open access to these files.
Associated Publications
Chen H, Ho Y, Mezzadra R, Adrover J, Smolkin R, Zhu C, Woess K, Bernstein N, Schmitt G, Fong L, Luan W, Wuest A, Tian S, Li X, Broderick C, Hendrickson R, Egeblad M, Chen Z, Alonso-Curbelo D, Lowe S. Senescence rewires microenvironment sensing to facilitate antitumor immunity. Cancer Discovery. 2023; 13(2):432-453.
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Dataset Format(s)
CSV
Dataset Size
2.4 MB
Data Catalog Record Updated
2024-01-09