Ceramide metabolism alterations contribute to Tumor Necrosis Factor-induced melanoma dedifferentiation and predict resistance to immune checkpoint inhibitors in advanced melanoma patients.

ABSTRACT:

Introduction

Advanced cutaneous melanoma is a skin cancer characterized by a poor prognosis and high metastatic potential. During metastatic spread, melanoma cells often undergo dedifferentiation toward an invasive phenotype, resulting in reduced expression of microphthalmia-associated transcription factor (MITF)-dependent melanoma antigens and facilitating immune escape. Tumor Necrosis Factor (TNF) is known to be a key factor in melanoma dedifferentiation. Interestingly, accumulating evidence suggests that TNF may play a role in melanoma progression and resistance to immunotherapies. Additionally, TNF has been identified as a potent regulator of sphingolipid metabolism, which could contribute to melanoma aggressiveness and the process of melanoma dedifferentiation.

Methods

SUBMITTER: Dufau C 

PROVIDER: S-EPMC11317267 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature