Pathogenesis of cutaneous T-cell lymphoma: Malignant inflammation, immune reprogramming, and microenvironmental drivers.

Cutaneous T-cell lymphomas, namely mycosis fungoides and Sézary syndrome, arise through a complex interplay of genetic alterations, epigenetic deregulation, immune imbalance, and tumor-microenvironment interactions. A progressive T helper 1-to-T helper 2 shift and chemokine-directed trafficking promote immune evasion and sustained malignant T-cell activity, whereas emerging data show subclonal diversity enabling adaptation to microenvironmental and therapeutic pressures. Skin-resident immune cells further shape disease behavior, and Staphylococcus aureus superantigens act as microenvironmental amplifiers that enhance malignant signaling and contribute to treatment resistance. A deeper understanding of how these molecular, immunological, and microbiome factors converge is essential to develop more precise, biomarker-informed therapeutic strategies.