© Saire Edith Córdova Hernández
Cutaneous T-cell lymphoma (CTCL) is a rare and aggressive form of non-Hodgkin lymphoma with poor prognosis and limited treatment options. The most prevalent subtypes: Mycosis Fungoides (MF) and Sézary Syndrome (SS), disrupt normal skin architecture, leading to chronic lesions and dermal tumors.
In this preclinical study, SeAx and MyLa cell lines were used to evaluate antitumor effects of mogamulizumab, pembrolizumab, and ruxolitinib, both as monotherapies and in combination: pembrolizumab+ruxolitinib and mogamulizumab+ruxolitinib.
In vitro, cell viability was assessed using Trypan Blue and Presto Blue assays; apoptosis was detected through Caspase 3/7 activity; migration and invasion capacities were analyzed using transwell assays, including transendothelial models with HUVEC monolayers. Furthermore, three-dimensional spheroids were generated to simulate tumor environment.
For in vivo studies, fertilized chicken embryos were inoculated with cancer cells in the chorioallantoic membrane (CAM). RT-qPCR targeting human Alu sequences was performed to detect metastatic dissemination in the CAM and distal organs such as liver, lung, and brain. Tumor cells present in the CAM were visualized by fluorescent microscopy; Western blot analysis of CAM-derived tumors was performed to evaluate pERK expression.
Results have shown that combined treatments significantly reduced cell viability, enhanced apoptosis and decreased migratory and invasive capacities compared to monotherapies. In vivo, these treatment combinations markedly reduced metastatic burden, as evidenced by lower cancer cell detection in CAM and distal organs.
Altogether, these relevant novel findings support the therapeutic potential of combining immunotherapy (anti-PD-1, anti-CCR4) with JAK inhibition as a promising treatment approach for CTCL, warranting further preclinical and clinical investigation.
