CD4 T cells kill melanoma cells by mechanisms that are independent of Fas (CD95)

Int J Cancer. 1998 Jan 30;75(3):384-90. doi: 10.1002/(sici)1097-0215(19980130)75:3<384::aid-ijc10>3.0.co;2-9.

Abstract

Previous studies have shown that CD4 T cells are associated with regression in primary melanoma and rejection of tumors in adoptive transfer models. The mechanism by which they mediate their anti-tumor effects remains unclear, and some studies have suggested that Fas ligand (FasL)/Fas interactions were involved. In the present study, we have examined the cytotoxic mechanism involved in CD4 T-cell killing of melanoma cells and, in particular, the role of FasL/Fas interactions in this killing. We show that the CD4 T cells in 4 clones of T cells induced apoptosis in autologous melanoma cells by MHC-restricted mechanisms but lysed an allogeneic melanoma cell by a non-apoptotic mechanism. Melanoma cells expressed both Fas and FasL, but killing of melanoma cells did not involve Fas/FasL interactions. This was shown by a lack of correlation between Fas expression and susceptibility to lysis and by failure of a monoclonal antibody to Fas to block killing by the CD4 T cells, though the latter expressed FasL. Recombinant FasL did not induce killing of melanoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Base Sequence
  • CD4-Positive T-Lymphocytes / immunology*
  • Calcium / metabolism
  • Cell Cycle
  • Cytotoxicity, Immunologic
  • Humans
  • Immunotherapy, Adoptive*
  • Major Histocompatibility Complex / immunology
  • Male
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Melanoma / therapy*
  • Middle Aged
  • Molecular Sequence Data
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured
  • fas Receptor / physiology*

Substances

  • fas Receptor
  • Calcium

Associated data

  • GENBANK/U08137