RET and cancer: Conversely, a multi-cancer study which included melanoma samples linked RET mutations to favorable immunotherapy outcomes, characterized by an increase in cytotoxic T cell infiltration and upregulation of immune checkpoints such as CTLA-4, PD-1 and PD-L1 (60) Thus, the precise role of RET S649L in sporadic CM, including its impact on tumor progression, immunotherapy response, and its viability as an actionable target in this setting, remains unknown, and further studies are needed.