Phototherapy-induced interferon kappa drives type I interferon mediated anticancer responses in cutaneous T cell lymphoma. (October 2021)

• Record Type: Journal Article
• Authors: Yu, Zizi; Vieyra-Garcia, Pablo; Benezeder, Theresa; Crouch, Jack; O'Malley, John; Devlin, Phillip; Gehad, Ahmed; Zhan, Qian; Gudjonsson, Johann; Sarkar, Mrinal; Kahlenberg, Michelle; Gerard, Nega; Teague, Jessica; Kupper, Thomas; Leboeuf, Nicole; Larocca, Cecelia; Tawa, Marianne; Wolf, Peter; Clark, Rachael
• Is Part Of: European journal of cancer. Volume 156(2021)Supplement 1
• Page Start: S21
• Publication Date: 2021-10
• Subjects: Phototherapy -- immunotherapy -- interferon; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/S0959-8049(21)00665-1
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract : Phototherapy is a T cell immunosuppressive therapy that effectively treats inflammatory skin diseases and improves cutaneous T cell lymphoma by unclear mechanisms. We observed defective type I interferon production in untreated CTCL skin lesions. Effective tumor clearance was associated with upregulation of type I interferon production, increased recruitment of CD8 T cells into tumors and gene expression changes characteristic of antigen specific T cell activation. Malignant T cell numbers in skin were associated with increased expression of IRF2, a negative regulator of interferon production. Phototherapy increased gene and protein expression of interferon kappa, a UVB inducible up-regulator of type I interferon production. In vitro, UVA exposure induced production of interferon kappa by human keratinocytes that preceded upregulation of other type I interferons. Keratinocytes deficient in interferon kappa had decreased baseline and induced type I interferon expression in response to UVA. In summary, we find that phototherapy up regulates keratinocyte interferon kappa production, leading to enhanced type I interferon production and improved anticancer responses. These studies demonstrate a baseline deficit in type I interferon production in CTCL and suggest a role for interferon kappa in the mechanism of action of phototherapy.