Immune checkpoint blockades therapy of melanoma.

Melanoma,a type of skin malignancy with a high incidence and poor prognosis,is a global public health issue.The tumorigenesis and pathogenesis of melanoma involve genetic mutations,meta-bolic disruption,and immune evasion.Tumors undergo immune editing to escape immune surveillance,and immune escape has been identified as a critical factor in the development and progres-sion of melanoma.Therefore,the blockade against immune check-points,including antibodies targeting programmed cell death protein 1/ligand 1(anti-PD-1/PD-L1)and cytotoxic T-lympho-cyte-associated antigen 4(anti-CTLA-4),has shown considerable clinical benefits in patients with advanced and inoperable mela-noma(Supplementary Text 1 online).Despite showing a consider-able effect in the treatment of melanoma,immune checkpoint blockade(ICB)therapy still has limitations,including low response rates,drug resistance,and immune-related adverse events(irAEs)(Supplementary Text 2 online).These limitations may burden patients with advanced tumors and poor survival.This paper aims to review the current bottlenecks in clinical application,research advances in ICB therapy,and future therapeutic possibilities.