The metabolic milieu in melanoma: Role of immune suppression by CD73/adenosine

The mechanisms leading to immune escape of melanoma have been largely investigated in relation to its tumour immunogenicity and features of inflamed microenvironment that promote the immune suppression during the disease progression. These findings have recently led to advantages in terms of immunotherapy-based approaches as rationale for overcoming the immune escape. However, besides immune checkpoints, other mechanisms including the adenosine produced by ectonucleotidases CD39 and CD73 contribute to the melanoma progression due to the immunosuppression induced by the tumour milieu. On the other hand, CD73 has recently emerged as both promising therapeutic target and unfavourable prognostic biomarker. Here, we review the major mechanisms of immune escape activated by the CD39/CD73/adenosine pathway in melanoma and focus potential therapeutic strategies based on the control of CD39/CD73 downstream adenosine receptor signalling. These evidences provide the basis for translational strategies of immune combination, while CD73 would serve as potential prognostic biomarker in metastatic melanoma.