Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion.

Détails

ID Serval
serval:BIB_324086550512
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion.
Périodique
Science
Auteur⸱e⸱s
Zeng Q., Saghafinia S., Chryplewicz A., Fournier N., Christe L., Xie Y.Q., Guillot J., Yucel S., Li P., Galván J.A., Karamitopoulou E., Zlobec I., Ataca D., Gallean F., Zhang P., Rodriguez-Calero J.A., Rubin M., Tichet M., Homicsko K., Hanahan D.
ISSN
1095-9203 (Electronic)
ISSN-L
0036-8075
Statut éditorial
Publié
Date de publication
18/11/2022
Peer-reviewed
Oui
Volume
378
Numéro
6621
Pages
eabl7207
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Many human cancers manifest the capability to circumvent attack by the adaptive immune system. In this work, we identified a component of immune evasion that involves frequent up-regulation of fragile X mental retardation protein (FMRP) in solid tumors. FMRP represses immune attack, as revealed by cancer cells engineered to lack its expression. FMRP-deficient tumors were infiltrated by activated T cells that impaired tumor growth and enhanced survival in mice. Mechanistically, FMRP's immunosuppression was multifactorial, involving repression of the chemoattractant C-C motif chemokine ligand 7 (CCL7) concomitant with up-regulation of three immunomodulators-interleukin-33 (IL-33), tumor-secreted protein S (PROS1), and extracellular vesicles. Gene signatures associate FMRP's cancer network with poor prognosis and response to therapy in cancer patients. Collectively, FMRP is implicated as a regulator that orchestrates a multifaceted barrier to antitumor immune responses.
Mots-clé
Animals, Humans, Mice, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Immune Evasion, Neoplasms/immunology, Immune Tolerance, Chemokine CCL7/metabolism, Interleukin-33, Protein S/metabolism
Pubmed
Création de la notice
29/11/2022 8:30
Dernière modification de la notice
04/01/2023 6:50
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