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
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
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