112 Gene expression changes in sezary syndrome patients following mogamulizumab treatment refines biomarker and immune profile
نویسندگان
چکیده
Sezary syndrome (SS) is the leukemic variant of CD4+ cutaneous T-cell lymphoma. Mogamulizumab an FDA-approved monoclonal antibody targeting surface CCR4 on SS cells. We’ve previously described highly expressed biomarker genes and altered cytokine gene expression that favors a Th2-immune phenotype. Here we evaluated mogamulizumab’s efficacy in reducing malignant T-cells, decreasing expression, modulating to gain insight into cytologic functional immune changes following treatment. We analyzed peripheral blood mononuclear cells (PBMC) from 11 healthy donors (HD) 6 patients met CD4+/CD26- CD4+/ CD8+ diagnostic criteria. After mogamulizumab treatment, T-cells decreased CD4+/CD8+ ratio normalized all patients. Analysis pretreatment PBMC by qRT-PCR showed significant overexpression PLS3, TWIST1, KCNK1, TOX, DNM3, GATA3 compared HD. Post-treatment, 100% reduction levels were similar normal most genes. Only PLS3 KCNK1 remained significantly overexpressed Most increased STAT4 IFNG treatment (83% 67%, respectively). Cytokines IL17A, IL4, IL10 reduced 67% IL13 was 50% IL2 33% correlated with (r = 0.8217, p 0.0010). In conclusion, demonstrated effective number CTCL, rapidly downregulated Th2-associated STAT4. This study provides further detailed molecular responses during identifies may reflect meaningful alterations. Together, these markers could be important classification patient disease response.
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2022
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2022.05.047