Alaimo, Alessandro; Genovesi, Sacha; Annesi, Nicole; De Felice, Dario; Subedi, Saurav; Macchia, Alice; La Manna, Federico; Ciani, Yari; Vannuccini, Federico; Mugoni, Vera; Notarangelo, Michela; Libergoli, Michela; Broso, Francesca; Taulli, Riccardo; Ala, Ugo; Savino, Aurora; Cortese, Martina; Mirzaaghaei, Somayeh; Poli, Valeria; Bonapace, Ian Marc; ... (2024). Sterile inflammation via TRPM8 RNA-dependent TLR3-NF-kB/IRF3 activation promotes antitumor immunity in prostate cancer. The EMBO journal, 43(5), pp. 780-805. EMBO Press 10.1038/s44318-024-00040-5
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alaimo-et-al-2024-sterile-inflammation-via-trpm8-rna-dependent-tlr3-nf-kb-irf3-activation-promotes-antitumor-immunity.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (5MB) | Preview |
Inflammation is a common condition of prostate tissue, whose impact on carcinogenesis is highly debated. Microbial colonization is a well-documented cause of a small percentage of prostatitis cases, but it remains unclear what underlies the majority of sterile inflammation reported. Here, androgen- independent fluctuations of PSA expression in prostate cells have lead us to identify a prominent function of the Transient Receptor Potential Cation Channel Subfamily M Member 8 (TRPM8) gene in sterile inflammation. Prostate cells secret TRPM8 RNA into extracellular vesicles (EVs), which primes TLR3/NF-kB-mediated inflammatory signaling after EV endocytosis by epithelial cancer cells. Furthermore, prostate cancer xenografts expressing a translation-defective form of TRPM8 RNA contain less collagen type I in the extracellular matrix, significantly more infiltrating NK cells, and larger necrotic areas as compared to control xenografts. These findings imply sustained, androgen-independent expression of TRPM8 constitutes as a promoter of anticancer innate immunity, which may constitute a clinically relevant condition affecting prostate cancer prognosis.
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