Analysis of expression of the melanoma-associated antigens MART-1 and gp 100 in metastatic melanoma cell lines and in in situ lesions

Francesco M. Marincola, Yasmine M. Hijazi, Patricia Fetsch, Michael L. Salgaller, Licia Rivoltini, Janice Cormier, Toni B. Simonis, Paul H. Duray, Meenhard Herlyn, Yutaka Kawakami, Steven A. Rosenberg

研究成果: Article査読

130 被引用数 (Scopus)

抄録

MART-1 and gp100 melanoma associated antigens (MAA) are expressed by cells of the melanocytic lineage and are recognized by the majority of HLA-A2 restricted tumor-infiltrating lymphocytes. Heterogeneity of expression of MAA in tumor deposits may affect the natural history or response to therapy of patients with melanoma. In this study, we evaluated the expression of these MAA with a new monoclonal antibody (mAb) directed against MART-1 (M2-7C10) and the commercially available HMB45 mAb directed against gp100. Expression was tested in vitro by intracellular fluorescence analysis and in vivo by immunophenotyping of tissue specimens. Nine melanoma cell lines and 25 tissue specimens from metastatic melanoma were analyzed. One cell line did not express MART-1 or gp100. The expression of both antigens was more heterogeneous and significantly reduced (p<0.01) in melanoma cell lines compared with melanocytes, suggesting progressive loss of expression of MAA by neoplastic cells. None of the nonmelanoma cancer lines tested stained for MART-1 or gp100. Analysis of melanoma lesions by immunohistochemistry showed significant heterogeneity of expression of both MART-1 and gp100 MAA either as a percentage of cells expressing MAA or as intensity of expression. Ten of 25 frozen sections expressed MART-1 in <50% of the cells. In 6 of 25 lesions, immunoreactivity for MART-1 was totally absent. Fine needle aspiration of metastatic lesions seemed to yield information accurately about amount and heterogeneity of expression of MAA in tumor lesions in vivo. Heterogeneity of expression of MAA may be one of several mechanisms leading to tumor escape from immune recognition, and pretreatment evaluation of tumor lesion for expression of these antigens may help in selecting patients best suited to antigen-specific vaccine therapies.

本文言語English
ページ(範囲)192-205
ページ数14
ジャーナルJournal of Immunotherapy
19
3
DOI
出版ステータスPublished - 1996 1 1

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学
  • 薬理学
  • 癌研究

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