Abstract
The appearance of human leukocyte antigen (HLA) class II antigens may be associated with malignant transformation of melanocytes. However, the information available regarding the clinical relevance of HLA class II antigen expression, which has been found in approximately 50% of primary and metastatic cutaneous melanoma lesions, is scarce and conflicting. The debate regarding the clinical relevance of HLA class II antigen expression by malignant melanocytes, in conjunction with our increased understanding of HLA class II antigen processing and presentation, their role in the interactions between melanoma cells and components of the adaptive immune system and their potential involvement in melanoma cell migration have provided the impetus to revisit the topic of HLA class II antigen expression by malignant melanocytes. This review will discuss the current knowledge regarding HLA class II antigens, including the presentation pathway; frequency of expression in cell lines and lesions of melanocytic origin; potential molecular mechanisms involved in such expression; potential role in the biology of melanoma cells and their interaction with components of the adaptive immune system; and, lastly, the potential clinical significance of HLA class II antigen expression in melanoma lesions and the variables that may confound such assessment.
Acknowledgements
This work was supported by PHS grants RO1 CA67108 and T32 CA85183 awarded by National Cancer Institute, DHHS and by Department of Defense predoctoral fellowship BC030039.
Notes
ARE: Activating response element; CIITA: Class II transactivator protein; HLA: Human leukocyte antigen; IFN: Interferon; IL: Interleukin; TNF: Tumor necrosis factor.
CAMEL: Cytotoxic T lymphocyte-recognized antigen on melanoma; hTRT: Human telomerase reverse transcriptase; MAGE: Melanoma antigen; MART: Melanoma antigen recognized by T cells; MUC1: Mucin 1; NY-ESO: New York esophageal squamous cell carcinoma; RAS: Rat sarcoma oncogene; TRP: Tyrosinase-related protein.