Common expression of melanoma tumor-associated antigens recognized by human tumor infiltrating lymphocytes: Analysis by human lymphocyte antigen restriction

Sophia S. Horn, Suzanne L. Topalian, Toni Simonis, Marie Mancini, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

Major histocompatibility complex (MHC) class I antigens (Ag), particularly human lymphocyte antigen (HLA)-A2, have been shown to function as restriction elements in human cytotoxic T lymphocyte recognition of tumor. This study was undertaken to determine the function of non-A2 MHC class I Ag in tumor recognition by tumor-infiltrating lymphocytes (TILs) cultured from six melanomas, and to find evidence for shared or unique tumorassociated Ag. Four predominantly CD8+ and two mixed CD4+, CD8+ population TIL cultures were tested for lysis in short-term 51Cr-release assays against a panel of targets including 29 fresh melanomas, 2 fresh sarcomas, 11 cultured melanoma lines, and 14 nonmelanoma cell lines derived from HLA-typed patients. All six melanoma TILs lysed the autologous melanoma. Two of three TILs from HLA-A2+ patients lysed allogeneic melanomas matched for HLA-A2, giving evidence for shared tumor Ag; one of these TILs also used HLA-B44 as a restriction element. The third HLA-A2+ TIL lysed autologous melanoma but not autologous Epstein-Barr virus-transformed B cells nor 14 HLA-A2 matched allogeneic melanomas, suggesting the possibility of a unique tumor Ag in this system. The three HLA-A2- TILs each lysed multiple HLA-matched melanomas, using HLA-A24, HLA-A31, and HLA-Cw7 as restriction elements. Blocking of autologous and allogeneic melanoma lysis by TILs with mAb w6/32 (anti-MHC class I) and anti-CD3, as well as cold target inhibition assays, confirmed that specific interaction of the T-cell receptor with MHC class I Ag and the relevant tumor Ag on the target cell surface is required for tumor lysis. These data provide evidence for specific recognition of shared melanoma Ag by human TILs.

Original languageEnglish (US)
Pages (from-to)153-164
Number of pages12
JournalJournal of Immunotherapy
Volume10
Issue number3
StatePublished - Jun 1991

Keywords

  • Immunotherapy
  • Major histocompatibility complex restriction
  • Melanoma
  • Tumor antigen
  • Tumor infiltrating lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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