{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yu Z"],"funding":["NCI NIH HHS","NIAMS NIH HHS"],"pagination":["621-632.e1"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922223"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["144(3)"],"pubmed_abstract":["Transcriptional profiling demonstrated markedly reduced type I IFN gene expression in untreated mycosis fungoides (MF) skin lesions compared with that in healthy skin. Type I IFN expression in MF correlated with antigen-presenting cell-associated IRF5 before psoralen plus UVA therapy and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I IFN production in MF and increased levels after psoralen plus UVA treatment in responding patients. Effective tumor clearance was associated with increased type I IFN expression, enhanced recruitment of CD8<sup>+</sup> T cells into skin lesions, and expression of genes associated with antigen-specific T-cell activation. IFNk, a keratinocyte-derived inducer of type I IFNs, was increased by psoralen plus UVA therapy and expression correlated with upregulation of other type I IFNs. In vitro, deletion of keratinocyte IFNk decreased baseline and UVA-induced expression of type I IFN and IFN response genes. In summary, we find a baseline deficit in type I IFN production in MF that is restored by psoralen plus UVA therapy and correlates with enhanced antitumor responses. This may explain why MF generally develops in sun-protected skin and suggests that drugs that increase epithelial type I IFNs, including topical MEK and EGFR inhibitors, may be effective therapies for MF."],"journal":["The Journal of investigative dermatology"],"pubmed_title":["Phototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides."],"pmcid":["PMC10922223"],"funding_grant_id":["U01 CA253190","R01 AR065807","P30 AR069625","T32 AR007098","R01 CA203721","R01 AR074797","P30 AR075043"],"pubmed_authors":["Pomahac B","Kahlenberg JM","Tawa M","Gudjonsson JE","Larocca C","Wolf P","Devlin PM","Crouch JD","Sarkar MK","Vieyra-Garcia P","Kim IR","Benezeder T","Gerard N","Orgill DP","LeBoeuf NR","Clark RA","Gehad A","O'Malley JT","Zhan Q","Kupper TS","Yu Z","Teague JE","Talbot SG"],"additional_accession":[]},"is_claimable":false,"name":"Phototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.","description":"Transcriptional profiling demonstrated markedly reduced type I IFN gene expression in untreated mycosis fungoides (MF) skin lesions compared with that in healthy skin. Type I IFN expression in MF correlated with antigen-presenting cell-associated IRF5 before psoralen plus UVA therapy and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I IFN production in MF and increased levels after psoralen plus UVA treatment in responding patients. Effective tumor clearance was associated with increased type I IFN expression, enhanced recruitment of CD8<sup>+</sup> T cells into skin lesions, and expression of genes associated with antigen-specific T-cell activation. IFNk, a keratinocyte-derived inducer of type I IFNs, was increased by psoralen plus UVA therapy and expression correlated with upregulation of other type I IFNs. In vitro, deletion of keratinocyte IFNk decreased baseline and UVA-induced expression of type I IFN and IFN response genes. In summary, we find a baseline deficit in type I IFN production in MF that is restored by psoralen plus UVA therapy and correlates with enhanced antitumor responses. This may explain why MF generally develops in sun-protected skin and suggests that drugs that increase epithelial type I IFNs, including topical MEK and EGFR inhibitors, may be effective therapies for MF.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-22T18:46:42.988Z","creation":"2025-04-06T02:36:04.888Z"},"accession":"S-EPMC10922223","cross_references":{"pubmed":["37716650"],"doi":["10.1016/j.jid.2023.06.212"]}}