| Autor: |
Theresa Benezeder, Rachael A. Clark, J. Crouch, Pablo A. Vieyra-Garcia, Nicole R. LeBoeuf, Peter Wolf, A. Gehad, Johann E. Gudjonsson, Mrinal K. Sarkar, Cecelia Larocca, Marianne Tawa, John T. O'Malley, Qian Zhan, Phillip M. Devlin, Jessica E. Teague, M. Kahlenberg, Nega Gerard, Thomas S. Kupper, Zizi Yu |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
European Journal of Cancer. 156:S21 |
| ISSN: |
0959-8049 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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