biostudies-literatureYu ZNCI NIH HHSNIAMS NIH HHS621-632.e1https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922223biostudies-literatureUnknown144(3)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⁺ 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.The Journal of investigative dermatologyPhototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.PMC10922223U01 CA253190R01 AR065807P30 AR069625T32 AR007098R01 CA203721R01 AR074797P30 AR075043Pomahac BKahlenberg JMTawa MGudjonsson JELarocca CWolf PDevlin PMCrouch JDSarkar MKVieyra-Garcia PKim IRBenezeder TGerard NOrgill DPLeBoeuf NRClark RAGehad AO'Malley JTZhan QKupper TSYu ZTeague JETalbot SGfalsePhototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.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⁺ 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.2024-01-01T00:00:00Z2024 Mar2025-04-22T18:46:42.988Z2025-04-06T02:36:04.888ZS-EPMC109222233771665010.1016/j.jid.2023.06.212