Article ; Online: Microenvironment-dependent growth of Sezary cells in humanized IL-15 mice.
2023 Volume 16, Issue 10
Abstract: Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small-animal models. Here, we demonstrate that IL-15 is a critical CTCL growth factor. Importantly, ...
| Abstract | Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small-animal models. Here, we demonstrate that IL-15 is a critical CTCL growth factor. Importantly, an immunodeficient knock-in mouse model genetically engineered to express human IL-15 uniquely supported the growth of SS patient samples relative to conventional immunodeficient mouse strains. SS patient-derived xenograft (PDX) models recapacitated key pathological features of the human disease, including skin infiltration and spread of leukemic cells to the periphery, and maintained the dependence on human IL-15 upon serial in vivo passaging. Detailed molecular characterization of the engrafted cells by single-cell transcriptomic analysis revealed congruent neoplastic gene expression signatures but distinct clonal engraftment patterns. Overall, we document an important dependence of Sezary cell survival and proliferation on IL-15 signaling and the utility of immunodeficient humanized IL-15 mice as hosts for SS - and potentially other T and NK cell-derived hematologic malignancies - PDX model generation. Furthermore, these studies advocate the thorough molecular understanding of the resultant PDX models to maximize their translational impact. |
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| MeSH term(s) | Humans ; Animals ; Mice ; Skin Neoplasms/metabolism ; Interleukin-15 ; Lymphoma, T-Cell, Cutaneous/pathology ; Sezary Syndrome/metabolism ; Sezary Syndrome/pathology ; Lymphocytes/metabolism ; Tumor Microenvironment |
| Chemical Substances | Interleukin-15 |
| Language | English |
| Publishing date | 2023-10-13 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2451104-3 |
| ISSN | 1754-8411 ; 1754-8403 |
| ISSN (online) | 1754-8411 |
| ISSN | 1754-8403 |
| DOI | 10.1242/dmm.050190 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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