| http://purl.uniprot.org/citations/33690225 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33690225 | http://www.w3.org/2000/01/rdf-schema#comment | "Melanomas commonly undergo a phenotype switch, from a proliferative to an invasive state. Such tumor cell plasticity contributes to immunotherapy resistance; however, the mechanisms are not completely understood and thus are therapeutically unexploited. Using melanoma mouse models, we demonstrated that blocking the MNK1/2-eIF4E axis inhibited melanoma phenotype switching and sensitized melanoma to anti-PD-1 immunotherapy. We showed that phospho-eIF4E-deficient murine melanomas expressed high levels of melanocytic antigens, with similar results verified in patient melanomas. Mechanistically, we identified phospho-eIF4E-mediated translational control of NGFR, a critical effector of phenotype switching. Genetic ablation of phospho-eIF4E reprogrammed the immunosuppressive microenvironment, exemplified by lowered production of inflammatory factors, decreased PD-L1 expression on dendritic cells and myeloid-derived suppressor cells, and increased CD8+ T cell infiltrates. Finally, dual blockade of the MNK1/2-eIF4E axis and the PD-1/PD-L1 immune checkpoint demonstrated efficacy in multiple melanoma models regardless of their genomic classification. An increase in the presence of intratumoral stem-like TCF1+PD-1+CD8+ T cells, a characteristic essential for durable antitumor immunity, was detected in mice given a MNK1/2 inhibitor and anti-PD-1 therapy. Using MNK1/2 inhibitors to repress phospho-eIF4E thus offers a strategy to inhibit melanoma plasticity and improve response to anti-PD-1 immunotherapy."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci140752"xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Benoit A."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Gagnon N."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Su J."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Yang W."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Zhan Y."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Sonenberg N."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Topisirovic I."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Guo Q."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Huang F."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Del Rincon S.V."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Rudd C.E."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Faber J."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Rzymski T."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Krawczyk C.M."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Dankort D."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Goncalves C."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Miller W.H. Jr."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Saragovi H.U."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Ghanem G.E."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Mazan M."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Attias M."xsd:string |
| http://purl.uniprot.org/citations/33690225 | http://purl.uniprot.org/core/author | "Galan A."xsd:string |