Zeng, QiqunSaghafinia, SadeghChryplewicz, Agnieszka AlicjaFournier, NadineChriste, LucineXie, Yu-QingGuillot, JeremyYucel, SimgeLi, PuminGalvan, Jose A.Karamitopoulou, EvaZlobec, IntiAtaca, DalyaGallean, FleurianeZhang, PengRodriguez-Calero, Jose AntonioRubin, MarkTichet, MelanieHomicsko, KrisztianHanahan, Douglas2024-03-182024-03-182024-03-182022-11-1810.1126/science.abl7207https://infoscience.epfl.ch/handle/20.500.14299/206389WOS:001161941200001Many 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.text::journal::journal article::research article