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

Autor: Zeng Q; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.; Opna Bio SA, Biopole, 1066 Epalinges, Lausanne, Switzerland., Saghafinia S; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.; Opna Bio SA, Biopole, 1066 Epalinges, Lausanne, Switzerland., Chryplewicz A; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.; Agora Cancer Research Center, 1011 Lausanne, Switzerland., Fournier N; Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland., Christe L; Institute of Pathology, University of Bern, 3008 Bern, Switzerland., Xie YQ; Institute of Bioengineering, School of Engineering, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland., Guillot J; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.; Agora Cancer Research Center, 1011 Lausanne, Switzerland., Yucel S; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.; Agora Cancer Research Center, 1011 Lausanne, Switzerland., Li P; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.; Agora Cancer Research Center, 1011 Lausanne, Switzerland.; Department of Computational Biology, University of Lausanne, 1015 Lausanne, Switzerland., Galván JA; Institute of Pathology, University of Bern, 3008 Bern, Switzerland., Karamitopoulou E; Institute of Pathology, University of Bern, 3008 Bern, Switzerland., Zlobec I; Institute of Pathology, University of Bern, 3008 Bern, Switzerland., Ataca D; Opna Bio SA, Biopole, 1066 Epalinges, Lausanne, Switzerland., Gallean F; Opna Bio SA, Biopole, 1066 Epalinges, Lausanne, Switzerland., Zhang P; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China., Rodriguez-Calero JA; Department for BioMedical Research, University of Bern, 3008 Bern, Switzerland., Rubin M; Department for BioMedical Research, University of Bern, 3008 Bern, Switzerland., Tichet M; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.; Agora Cancer Research Center, 1011 Lausanne, Switzerland.; Lausanne Branch, Ludwig Institute for Cancer Research, 1011 Lausanne, Switzerland., Homicsko K; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.; Agora Cancer Research Center, 1011 Lausanne, Switzerland.; Lausanne Branch, Ludwig Institute for Cancer Research, 1011 Lausanne, Switzerland.; Department of Oncology, University Hospital of Lausanne (CHUV), 1011 Lausanne, Switzerland.; Swiss Cancer Center Leman (SCCL), 1011 Lausanne, Switzerland., Hanahan D; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.; Agora Cancer Research Center, 1011 Lausanne, Switzerland.; Lausanne Branch, Ludwig Institute for Cancer Research, 1011 Lausanne, Switzerland.; Swiss Cancer Center Leman (SCCL), 1011 Lausanne, Switzerland.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Nov 18; Vol. 378 (6621), pp. eabl7207. Date of Electronic Publication: 2022 Nov 18.
DOI: 10.1126/science.abl7207
Abstrakt: 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.
Databáze: MEDLINE
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