Sterile inflammation via TRPM8 RNA-dependent TLR3-NF-kB/IRF3 activation promotes antitumor immunity in prostate cancer

被引：12

作者：

Alaimo, Alessandro ^{[1
]}

Genovesi, Sacha ^{[1
]}

Annesi, Nicole ^{[1
]}

De Felice, Dario ^{[1
]}

Subedi, Saurav ^{[2
]}

Macchia, Alice ^{[1
]}

La Manna, Federico ^{[2
]}

Ciani, Yari ^{[1
]}

Vannuccini, Federico ^{[1
]}

Mugoni, Vera ^{[1
]}

Notarangelo, Michela ^{[1
]}

Libergoli, Michela ^{[1
]}

Broso, Francesca ^{[1
]}

Taulli, Riccardo ^{[3
,4
]}

Ala, Ugo ^{[5
]}

Savino, Aurora ^{[6
]}

Cortese, Martina ^{[1
]}

Mirzaaghaei, Somayeh ^{[6
,7
]}

Poli, Valeria ^{[6
,7
]}

Bonapace, Ian Marc ^{[8
]}

Papotti, Mauro Giulio ^{[9
]}

Molinaro, Luca ^{[9
]}

Doglioni, Claudio ^{[10
]}

Caffo, Orazio ^{[11
]}

Anesi, Adriano ^{[12
]}

Nagler, Michael ^{[13
]}

Bertalot, Giovanni ^{[14
,15
]}

Carbone, Francesco Giuseppe ^{[14
]}

Barbareschi, Mattia ^{[14
,15
]}

Basso, Umberto ^{[16
]}

Dassi, Erik ^{[1
]}

Pizzato, Massimo ^{[1
]}

Romanel, Alessandro ^{[1
]}

Demichelis, Francesca ^{[1
]}

Kruithof-de Julio, Marianna ^{[2
,13
]}

Lunardi, Andrea ^{[1
]}

机构：

[1] Univ Trento, Dept Cellular Computat & Integrat Biol CIBIO, Trento, Italy

[2] Univ Bern, Dept BioMed Res, Urol Res Lab, Bern, Switzerland

[3] Univ Torino, Dept Oncol, Turin, Italy

[4] AOU Citta Salute & Sci Torino, Ctr Expt Res & Med Studies CeRMS, Turin, Italy

[5] Univ Torino, Dept Vet Sci, Turin, Italy

[6] Univ Torino, Dept Mol Biotechnol & Hlth Sci, Turin, Italy

[7] Univ Torino, Mol Biotechnol Ctr MBC Guido Tarone, Turin, Italy

[8] Univ Insubria, Dept Biotechnol & Life Sci, Busto Arsizio, Italy

[9] Univ Torino, Dept Pathol, Turin, Italy

[10] San Raffaele Univ, San Raffaele Sci Inst IRCCS Vita Salute, Pancreas Translat & Clin Res Ctr, Div Pathol, Milan, Italy

[11] Santa Chiara Hosp APSS, Med Oncol Dept, Trento, Italy

[12] Santa Chiara Hosp APSS, Operat Unit Clin Pathol, Trento, Italy

[13] Univ Bern, Bern Univ Hosp, Dept Urol, Inselspital, Bern, Switzerland

[14] Santa Chiara Hosp APSS, Operat Unit Anat Pathol, Trento, Italy

[15] Univ Trento, Ctr Med Sci, CISMed, Trento, Italy

[16] Ist Oncol Veneto IOV IRCCS, Dept Oncol, Oncol Unit 1, Padua, Italy

来源：

EMBO JOURNAL | 2024年 / 43卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

Prostate; Inflammation; TRP; PSA; Immunity; NF-KAPPA-B; GENE-EXPRESSION; SUPPRESSION; TISSUES; PROTEIN; DRIVES; GEO; YAP;

D O I：

10.1038/s44318-024-00040-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：780 / 805

页数：26

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