ArticleThe Journal of experimental medicine2024
Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Mechano-immunomodulatory biomaterials: From immune mechanosensing to translational design.Bioactive materials · 2026Review
- Repurposing rosmarinic acid as an anti-colorectal cancer agent through bolstering T cell anti-tumor immunity by enhancing activation of MEK1-mediated TCR signaling.Cancer immunology, immunotherapy : CII · 2026Article
- IL-21 enhances the cytotoxicity of intratumoral CD8+ T cells, improving radiation efficacy.JCI insight · 2026Article
- Akt/mTOR pathway-mediated CCNA1 regulation of radiotherapy resistance in nasopharyngeal carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- PIEZO2 in tumors: from mechanobiological switches to activity-targeted therapies.Journal of experimental & clinical cancer research : CR · 2025Review
- STYK1 as a targetable vulnerability enhances the efficacy of anti-PD-L1 therapy in pancreatic cancer.Journal of gastroenterology · 2025Article
- The dual role of Piezo1 in tumor cells and immune cells: a new target for cancer therapy.Frontiers in immunology · 2025Review
- Compressive stresses in cancer: characterization and implications for tumour progression and treatment.Nature reviews. Cancer · 2024Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Changes in mechanosensitive ion channels following radiation have seldom been linked to therapeutic sensitivity or specific factors involved in antitumor immunity. Here, in this study, we found that the mechanical force sensor, Piezo2, was significantly upregulated in tumor cells after radiation, and Piezo2 knockout in tumor cells enhanced tumor growth suppression by radiotherapy. Specifically, loss of Piezo2 in tumor cells induced their IL-15 expression via unleashing JAK2/STAT1/IRF-1 axis after radiation. This increase in IL-15 activates IL-15Rα on tumor-infiltrating CD8+ T cells, thereby leading to their augmented effector and stem cell-like properties, along with reduced terminal exhausted feature. Importantly, Piezo2 expression was negatively correlated with CD8 infiltration, as well as with radiosensitivity of patients with rectum adenocarcinoma receiving radiotherapy treatment. Together, our findings reveal that tumor cell-intrinsic Piezo2 induces radioresistance by dampening the IRF-1/IL-15 axis, thus leading to impaired CD8+ T cell-dependent antitumor responses, providing insights into the further development of combination strategies to treat radioresistant cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.