The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Open accessAbstract
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 liver cancer model in which senescence triggers CD8 T cell–mediated tumor rejection, we show that senescence also remodels the cell-surface proteome to alter how tumor cells sense environmental factors, as exemplified by type II interferon (IFNγ). Compared with proliferating cells, senescent cells upregulate the IFNγ receptor, become hypersensitized to microenvironmental IFNγ, and more robustly induce the antigen-presenting machinery—effects also recapitulated in human tumor cells undergoing therapy-induced senescence. Disruption of IFNγ sensing in senescent cells blunts their immune-mediated clearance without disabling the senescence state or its characteristic secretory program. 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. Significance: Our work uncovers an interplay between tissue remodeling and tissue-sensing programs that can be engaged by senescence in advanced cancers to render tumor cells more visible to the adaptive immune system. This new facet of senescence establishes reciprocal heterotypic signaling interactions that can be induced therapeutically to enhance antitumor immunity. See the interview with Direna Alonso-Curbelo, PhD, recipient of the inaugural Cancer Discovery Early Career Award: https://vimeo.com/992987447 See related article by Marin et al., p. 410. This article is highlighted in the In This Issue feature, p. 247
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SenNet recommendations for detecting senescent cells in different tissues
Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., et al. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00738-8 · Cited by 408
Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity
Marin, I., Boix, O., Garcia-Garijo, A., Sirois, I., Caballe, A., Zarzuela, E., Ruano, I., Attolini, C. S.-O., Prats, N., López-Domínguez, J. A., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0523 · Cited by 346
Cellular senescence and SASP in tumor progression and therapeutic opportunities
Dong, Z., Luo, Y., Yuan, Z., Tian, Y., Jin, T., & Xu, F. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02096-7 · Cited by 259
Senescence as a therapeutic target in cancer and age-related diseases
McHugh, D., Durán, I., & Gil, J. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01074-4 · Cited by 197
The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2
Chaib, S., López-Domínguez, J. A., Lalinde-Gutiérrez, M., Prats, N., Marin, I., Boix, O., García-Garijo, A., Meyer, K., Muñoz, M. I., Aguilera, M., et al. (2024) · Nature Cancer · doi:10.1038/s43018-023-00712-x · Cited by 114
Metadata
- Authors
- Chen, H.-A., Ho, Y.-J., Mezzadra, R., Adrover, J. M., Smolkin, R., Zhu, C., Woess, K., Bernstein, N., Schmitt, G., Fong, L., Luan, W., Wuest, A., Tian, S., Li, X., Broderick, C., Hendrickson, R. C., Egeblad, M., Chen, Z., Alonso-Curbelo, D., & Lowe, S. W.
- Venue
- Cancer Discovery
- Published
- 2022-10-27
- Volume
- 13
- Issue
- 2
- Pages
- 432-453
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W4307504158
- Cited by
- 230
- References
- 43
- FWCI
- 24.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Chen, H.-A., Ho, Y.-J., Mezzadra, R., Adrover, J. M., Smolkin, R., Zhu, C., Woess, K., Bernstein, N., Schmitt, G., Fong, L., Luan, W., Wuest, A., Tian, S., Li, X., Broderick, C., Hendrickson, R. C., Egeblad, M., Chen, Z., Alonso-Curbelo, D., & Lowe, S. W. (2023). Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-22-0528
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