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.
Pablo Vieyra-Garcia, Jack D. Crouch, John T. O’Malley, Edward W. Seger, Chao H. Yang, Jessica E. Teague, Anna Maria Vromans, Ahmed Gehad, Thet Su Win, Zizi Yu, Elizabeth L. Lowry, Jung-Im Na, Alain H. Rook, Peter Wolf, Rachael A. Clark
Title and authors | Publication | Year |
---|---|---|
Translational analysis reveals roles for resident and recruited T cell subsets in drug hypersensitivity reactions varying with reaction type
Pranali Shah, George Romar, Artur Manukyan, Wei-Che Ko, Pei-Chen Hsieh, Gustavo Velasquez, Elisa Schunkert, Xiaopeng Fu, Indira Guleria, Roderick Bronson, Kevin Wei, Abigail Waldman, Frank Vleugels, Marilyn Liang, Anita Giobbie-Hurder, Arash Mostaghimi, Birgitta Schmidt, Victor Barrera, Ruth K. Foreman, Manuel Garber, Sherrie Divito |
Journal of Clinical Investigation | 2024 |
Role of IL-4 and IL-13 in Cutaneous T Cell Lymphoma.
Mazzetto R, Miceli P, Tartaglia J, Ciolfi C, Sernicola A, Alaibac M |
2024 | |
LAIR1 prevents excess inflammatory tissue damage in S. aureus skin infection and Cutaneous T-cell Lymphoma
Dorando HK, Mutic EC, Tomaszewski KL, Tian L, Stefanov MK, Quinn CC, Veis DJ, Wardenburg JB, Musiek AC, Mehta-Shah N, Payton JE |
2024 | |
The Tumor Microenvironment as a Therapeutic Target in Cutaneous T Cell Lymphoma
Kwantwi LB, Rosen ST, Querfeld C |
Cancers | 2024 |