Bibliographic Details
| Title: |
Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas. |
| Authors: |
Fischer, Anja, Albert, Thomas K., Moreno, Natalia, Interlandi, Marta, Mormann, Jana, Glaser, Selina, Patil, Paurnima, de Faria, Flavia W., Richter, Mathis, Verma, Archana, Balbach, Sebastian T., Wagener, Rabea, Bens, Susanne, Dahlum, Sonja, Göbel, Carolin, Münter, Daniel, Inserte, Clara, Graf, Monika, Kremer, Eva, Melcher, Viktoria |
| Source: |
Nature Communications; 10/3/2024, Vol. 15 Issue 1, p1-18, 18p |
| Subject Terms: |
T-cell lymphoma, HISTONE deacetylase inhibitors, DNA methylation, TUMOR microenvironment, FATIGUE (Physiology) |
| Abstract: |
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here, we identify a subgroup, PTCL-NOSSMARCB1-, which is characterized by the lack of the SMARCB1 protein and occurs more frequently in young patients. Human and murine PTCL-NOSSMARCB1- show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development. Single-cell analyses of human and murine tumors revealed a rich and complex network of interactions between tumor cells and an immunosuppressive and exhausted tumor microenvironment (TME). In a drug screen, we identified histone deacetylase inhibitors (HDACi) as a class of drugs effective against PTCL-NOSSmarcb1-. In vivo treatment of mouse tumors with SAHA, a pan-HDACi, triggered remodeling of the TME, promoting replenishment of lymphoid compartments and reversal of the exhaustion phenotype. These results provide a rationale for further exploration of HDACi combination therapies targeting PTCL-NOSSMARCB1- within the TME. Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous and aggressive type of T-cell lymphoma. Here, the authors perform single-cell analyses of human and murine PTCL-NOS tumors, and identify a subtype defined by the loss of SMARCB1 that could be targeted with HDAC-inhibitor combination therapies. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
