Heterogeneous expression of melanoma-associated antigens and HLA-A2 in metastatic melanoma in vivo

Loss of single HLA Class I allospecificities in melanoma cells due to selective genomic abbreviations

“…This fits well with earlier data from Cormier et al, 42 who monitored immunohistochemically a total of 217 specimens from patients with MM for the presence of MAA and HLA Class I. Between 6% and 21% of the samples showed a loss of either HLA-A2 or Melan-A/gp100.…”

“…Between 6% and 21% of the samples showed a loss of either HLA-A2 or Melan-A/gp100. 42 In contrast to Wang et al, 22 both of our MM cell cultures were established directly from the excised malignant lesion and did not undergo any mutagenesis by ␥-irradiation or other factors, resulting in defects of the mRNA splicing machinery. 43 Therefore, we feel encouraged to assume that the observed HLA-A2 losses in our melanoma cell cultures had in fact occurred in vivo.…”

Melanoma antigen expression in serial fine-needle aspiration samples in patients with metastatic malignant melanoma participating in immunotherapy clinical trials

“…Clinical trials using immunodominant peptides from melanoma associated antigens and recombinant adenoviruses coding human MAA for the treatment of patients with melanoma are ongoing at the NCI. [1][2][3][4][5][6][7][8][9] Melanoma antigens associated with HLA-A*0201, 11,12 which include MART-1/Melan A, 13,14 gp100/Pmel 17, 9 tyrosinase, 15 MAGE-3, 16 and N-acetylglucosaminyltransferase V, 17 are shared by most melanoma cells. The T-cell epitopes responsible for recognition of MAA have led to the development of vaccination pro- tocols based on the administration of short peptides representing such epitopes to patients with MMM.…”

“…Fine-needle aspiration allows for the sampling of the same metastatic lesion at various timepoints thereby enabling the direct evaluation of the therapy over time on any given lesion while the lesion remains in vivo. 1,[3][4][5] Peptide vaccination against melanoma antigens can produce a powerful systemic cytotoxic T-lymphocyte response. 9 It is theorized that antigen expression may be diminished due to selective immunodestruction of tumor cells, or perhaps intentionally, to escape immunosurveillance.…”

“…9 It is theorized that antigen expression may be diminished due to selective immunodestruction of tumor cells, or perhaps intentionally, to escape immunosurveillance. 3,4 Conversely, because MAAs are present on normal melanocytes as well as heterogeneously expressed in MMM, 1,10 these conditions could influence lack of recognition of the vaccine by the host immune system, resulting in the immunologic escape by the tumor cell.…”