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SHR Neuro Cancer Cardio Lipid Metab Microb

Yu, Z; Vieyra-Garcia, P; Benezeder, T; Crouch, JD; Kim, IR; O'Malley, JT; Devlin, PM; Gehad, A; Zhan, Q; Gudjonsson, JE; Sarkar, MK; Kahlenberg, JM; Gerard, N; Teague, JE; Kupper, TS; LeBoeuf, NR; Larocca, C; Tawa, M; Pomahac, B; Talbot, SG; Orgill, DP; Wolf, P; Clark, RA.
Phototherapy restores deficient type I interferon production and enhances antitumor responses in mycosis fungoides.
J Invest Dermatol. 2023; Doi: 10.1016/j.jid.2023.06.212 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Leading authors Med Uni Graz: Wolf Peter
Co-authors Med Uni Graz: Benezeder Theresa Helena; Vieyra Garcia Pablo Augusto
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Abstract:: Transcriptional profiling demonstrated markedly reduced type I interferon gene expression in untreated mycosis fungoides skin lesions compared to healthy skin. Type I interferon expression in MF correlated with APC-associated IRF5 before PUVA and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I interferon production in MF and increased levels post-PUVA in responding patients. Effective tumor clearance was associated with increased type I interferon expression, enhanced recruitment of CD8⁺ T cells into skin lesions and expression of genes associated with antigen specific T cell activation. Interferon kappa, a keratinocyte-derived inducer of type I interferons, was increased by PUVA and correlated with upregulation of other type I interferons. In vitro, deletion of keratinocyte interferon kappa decreased baseline and UVA-induced type I interferons and interferon response genes. In summary, we find a baseline deficit in type I interferon production in MF that is restored by PUVA 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 interferons, including topical MEK and EGFR inhibitors, may be effective therapies for MF.