A fresh look at an old story: revisiting HLA class II antigen expression by melanoma cells

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.Expert Rev. Dermatol. 1(6), 805-823 (2006) As in other types of cells in humans and in other animal species, malignant transformation of human melanocytes may be associated with changes in gene expression and in their antigenic profile [1]. Among the latter, changes in human leukocyte antigen (HLA) expression are of particular interest to tumor immunologists and clinical oncologists owing to the potential involvement of immunological events in the clinical course of melanoma [2] and owing to the crucial role played by HLA antigens in the interactions of tumor cells with the host's immune system [3][4][5][6]. Over the past 20 years, a number of studies have demonstrated that changes in HLA antigen expression occur frequently in melanoma lesions [1]. Most of these studies have focused on the analysis of HLA class I antigen expression by melanoma cells. This emphasis reflects the crucial role played by HLA class I antigens in the interactions of tumor cells with effector cells of the innate and adaptive immune system (i.e., CD8 + , HLA class I antigen-restricted, tumor antigen [TA]-specific cytotoxic T lymphocytes [CTLs] [3] and natural killer [NK] cells [4]). These studies have revealed that HLA class I antigen defects are found frequently in melanoma cells both in vitro and in vivo [1], and these defects are clinically significant [1], most likely because they provide tumor cells with a mechanism to escape immune cell recognition and destruction [1]. Interested readers are referred to recent reviews for additional information on HLA class I antigen defects in melanoma lesions and on their functional and clinical significance [1].Much less information is available regarding the functi...

Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T‐lymphocytes and preserved MHC class I antigen expression

“…Expression of MHC class II antigen in melanoma cells was detected in 25% of cases. Although controversial, most reports described that expression of MHC class II antigen is associated with an unfavorable outcome 44. No such association was observed in our series, but this might be caused by the relatively low number of cases studied.…”

A Comparison of HLA Genotype with Inflammation in Uveal Melanoma

“…These antigens have a crucial role in the induction of specific immune responses, and can modulate the interactions of natural killer (NK) cells and T cell subpopulations with their target cells. [2][3][4] The clinical relevance of HLA class I expression in oncology is evident from the finding that a reduced expression often correlates with a worse prognosis, [5][6][7][8][9][10] while the relevance of HLA class II expression in cancer remains ambivalent. 1,11,12 Unlike most tumors, in uveal melanoma a high HLA class I expression is considered to be a bad prognostic sign.…”