Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Vieyra-Garcia, P; Crouch, JD; O'Malley, JT; Seger, EW; Yang, CH; Teague, JE; Vromans, AM; Gehad, A; Win, TS; Yu, Z; Lowry, EL; Na, JI; Rook, AH; Wolf, P; Clark, RA.
Benign T cells drive clinical skin inflammation in cutaneous T cell lymphoma.
JCI Insight. 2019; 4(1):
Doi: 10.1172/jci.insight.124233
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Web of Science
PubMed
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- Leading authors Med Uni Graz
- Vieyra Garcia Pablo Augusto
- Wolf Peter
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- Abstract:
- Psoralen plus UVA (PUVA) is an effective therapy for mycosis fungoides (MF), the skin-limited variant of cutaneous T cell lymphoma (CTCL). In low-burden patients, PUVA reduced or eradicated malignant T cells and induced clonal expansion of CD8+ T cells associated with malignant T cell depletion. High-burden patients appeared to clinically improve but large numbers of malignant T cells persisted in skin. Clinical improvement was linked to turnover of benign T cell clones but not to malignant T cell reduction. Benign T cells were associated with the Th2-recruiting chemokine CCL18 before therapy and with the Th1-recruiting chemokines CXCL9, CXCL10, and CXCL11 after therapy, suggesting a switch from Th2 to Th1. Inflammation was correlated with OX40L and CD40L gene expression; immunostaining localized these receptors to CCL18-expressing c-Kit+ dendritic cells that clustered together with CD40+OX40+ benign and CD40+CD40L+ malignant T cells, creating a proinflammatory synapse in skin. Our data suggest that visible inflammation in CTCL results from the recruitment and activation of benign T cells by c-Kit+OX40L+CD40L+ dendritic cells and that this activation may provide tumorigenic signals. Targeting c-Kit, OX40, and CD40 signaling may be novel therapeutic avenues for the treatment of MF.