Cutaneous T-cell Lymphoma

P=N/A, N=10, Not yet recruiting, Assistance Publique - Hôpitaux de Paris

High frequencies of PD-L1+memory B cells, PD-1+DC and PD-1+naïve CD4+ T cells correlated with shorter progression-free survival, whereas normal levels of PD-1+transitional monocytes were associated with longer overall survival. Lesion-specific aberrant T cells and TME remodeling may drive MF severity and contribute to future immunotherapy.

P1, N=48, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

JAK1 and JAK3 were significantly expressed in MF skin lesions in comparison to normal controls. JAK1 and JAK3 were more expressed in the tumor stage than patch and plaque stage MF, suggesting that JAK1 and JAK3 could play a crucial role in MF pathogenesis, progression, and prognosis.

SE-producing S. aureus promotes skin barrier impairment in CTCL through cytokine-driven, JAK-dependent repression of structural proteins in keratinocytes. These findings identify microbial-immune crosstalk as a contributor to CTCL skin pathology and provide mechanistic rationale for strategies targeting S. aureus colonisation as adjunctive therapy in CTCL.

P1, N=42, Not yet recruiting, University of Pennsylvania

P1/2, N=18, Recruiting, Daihong Liu

This is one of the most comprehensive single-cell studies of leukaemic CTCL to date. We uncover new malignant T-cell states, broaden the known repertoire of KIR expression, and propose mechanisms of immune evasion that may contribute to treatment resistance. These findings lay the groundwork for subtype-specific and microenvironment-informed therapeutic strategies in Sézary syndrome, with potential implications for guiding targeted therapy selection but require validation in larger, independent cohorts.

P1, N=35, Not yet recruiting, Assistance Publique Hopitaux De Paris

Anti-apoptotic BCL2 was upregulated in all tumor cells from nonresponsive lesions, especially in CD30- subsets. We further confirmed a potent synergy between BV and BCL2 inhibitors in tumor cell lines, indicating a promising strategy to overcome resistance in CTCL.

These "avatar" models preserve vital tumor heterogeneity and microenvironmental context, offering superior predictive value. The systematic development and integration of these next-generation models are essential to bridge the translational gap and advance precision medicine for all patients with T-cell malignancies.