T-Cell recognition of human melanoma antigens

Yutaka Kawakami, Michael I. Nishimura, Nicholas P. Restifo, Suzanne L. Topalian, Bert H. O'Neil, Joel Shilyansky, John R. Yannelli, Steven A. Rosenberg

研究成果: Article査読

47 被引用数 (Scopus)

抄録

The adoptive transfer of tumor-infiltrating lymphocytes (TILs) with interleukin-2 (IL-2) has antitumor activity in some patients with metastatic melanoma. We have analyzed molecular mechanisms of TIL recognition of human melanoma. Some cultured TILs specifically lysed autologous and some allogeneic melanomas sharing a variety of class I major histocompatibility complex (MHC) molecules. HLA-A2—restricted melanoma-specific TILs lysed many HLA-A2+melanoma cell lines from different patients but failed to lyse HLA-A2melanoma and HLA-A2+nonmelanoma cell lines. However, these TILs were capable of lysing many naturally HLA-A2melanomas after introduction of the HLA-A2.1 gene by vaccinia virus. These results indicate that shared melanoma antigens (Ag) are expressed in melanomas regardless of their human leukocyte antigen types. In order to identify these shared melanoma Ags, we have tested some known proteins expressed in melanoma. Expression of tyrosinase or HMB45 Ag correlated with lysis of TILs. We are also attempting to isolate antigenic peptides by high performance liquid chromatography separation and genes encoding melanoma Ag by cDNA expression cloning. The T-cell component of the antimelanoma response was also analyzed by determining the genetic structure of the T-cell receptor (TCR) used by melanoma TILs. However, we did not observe common TCR variable region usage by different melanoma TILs. We could establish melanoma cell clones and lines resistant to TIL lysis due to the absence of or defects in the expression of Ag, MHC, or β2-microglobulin molecules. These data indicate multiple mechanisms for melanoma escape from T-cell immunosurveillance. These findings have important implications for the development of immunotherapies for melanoma.

本文言語English
ページ(範囲)88-93
ページ数6
ジャーナルJournal of Immunotherapy
14
2
DOI
出版ステータスPublished - 1993 8月
外部発表はい

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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