Type I and II IFNs Inhibit Merkel Cell Carcinoma via Modulation of the Merkel Cell Polyomavirus T Antigens

摘要: Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer associated with the polyomavirus (MCV). As MCC lines show oncogene addiction to MCV T antigens, pharmacologic interference of large antigen (LTA) may represent an effective therapeutic approach for this deadly cancer. In study, we investigated effects IFNs on lines, especially MCV-positive (MCV(+)) lines. Type I (i.e., Multiferon, mix different IFN-α subtypes, IFN-β) strongly inhibited cellular viability. Cell-cycle analysis showed increased sub-G fractions these cells upon IFN treatment indicating apoptotic death; were less pronounced IFN-γ. Notably, inhibitory effect type MCV(+) was reduced expression LTA as well promyelocytic leukemia (PML) protein, which known interfere function LTA. addition, intratumoral application Multiferon resulted in regression but not MCV(-) MCCs vivo. Together, our findings that have strong antitumor effect, at least part explained by modulation virally encoded