Beyond CD30: Dual-Targeting of Malignant and Regulatory T Cells by Brentuximab Vedotin Remodels the Lymphoma Microenvironment and Overcomes Resistance via BCL2 Inhibition in Mycosis Fungoides - PubMed
6 hours ago
- #Brentuximab vedotin
- #Mycosis Fungoides
- #BCL2 inhibition
- Brentuximab vedotin (BV) targets both CD30+ and CD30- malignant T cells in Mycosis Fungoides (MF), inducing immunogenic cell death (ICD).
- BV remodels the lymphoma microenvironment by targeting CD30+ tumor-infiltrating regulatory T cells (TI-Tregs) and activating anti-tumor immunity via dendritic cells and CD8+ T cells.
- Resistance to BV arises from upregulated drug efflux transporters, impaired endosomal processing in CD30+ cells, and blunted interferon responses in CD30- cells.
- Anti-apoptotic BCL2 is upregulated in nonresponsive lesions, particularly in CD30- tumor subsets.
- Combination therapy with BV and BCL2 inhibitors shows synergistic effects, offering a promising strategy to overcome resistance in cutaneous T cell lymphoma (CTCL).