THE UNDERSTANDING of mycosis fungoides (MF) and Sézary syndrome (SS) has advanced considerably in recent years, yet predicting disease progression and patient outcomes remains challenging. Researchers are now investigating T-cell receptor clonotype biomarkers as potential tools to better stratify patients and inform treatment decisions. A new retrospective cohort study of 125 patients provides fresh insight into how specific TCR gene patterns may correlate with disease severity and survival outcomes.
T-cell receptor clonotype biomarkers and disease progression
The study analysed skin biopsy samples from patients across early and advanced stages of MF/SS, using next-generation sequencing to identify dominant T-cell receptor β (TCRB) and γ (TCRG) gene clonotypes. Notably, two clonotypes stood out: Vb20 and Vg8. The presence of Vb20 was strongly associated with folliculotropism, a subtype that often coincides with large-cell transformation, which is typically linked to more aggressive disease. Patients carrying this clonotype also showed significantly poorer overall survival.
Similarly, the Vg8 clonotype was observed more frequently in patients with advanced-stage MF/SS compared to those with early-stage disease. The presence of Vg8 was also linked to reduced survival outcomes, reinforcing its potential role as a high-risk marker. These findings highlight the potential of T-cell receptor clonotype biomarkers to identify patients who may require closer monitoring or earlier escalation of therapy.
The study also noted that higher abundance of certain TCRG clonotypes correlated with increased expression of immune checkpoints, such as programmed cell death 1 (PD-1) and inducible T-cell costimulator (ICOS). This relationship may help explain variations in treatment response, particularly to immunotherapies.
Overall, the research suggests that incorporating T-cell receptor clonotype biomarkers into routine clinical assessment could significantly enhance risk stratification in MF/SS. Clinicians may be able to identify high-risk patients sooner and intervene with more aggressive or targeted therapies before the disease progresses. As precision medicine continues to evolve, these biomarkers could play a crucial role in improving patient outcomes and guiding future therapeutic strategies.
Reference
Crisan LL et al. T-cell receptor clonotypes and aggressive subtypes in cutaneous t-cell lymphoma. JAMA Dermatol. 2025;DOI:10.1001/jamadermatol.2025.4081.
