Drug resistance results in alterations in expression of immune recognition molecules and failure to express Fas (CD95)

Immunol Cell Biol. 1998 Aug;76(4):350-6. doi: 10.1046/j.1440-1711.1998.00758.x.

Abstract

It is demonstrated that methotrexate/cisplatin-sensitive L1210 cells express low levels of major histocompatibility complex (MHC) class II relative to the high levels expressed on methotrexate (MTX)/cisplatin-resistant L1210/DDP cells. L1210 cells express cell-surface Fas, while the L1210/DDP cells express no cell-surface Fas. Expression of costimulatory molecules B7-1/B7-2 and Fas is increased on L1210 cells, but not L1210/DDP, in the presence of methotrexate or trimetrexate (TMTX). Therefore, a component of the mechanism of action of some anti-cancer agents may be to facilitate immune recognition and T cell-directed, Fas-induced cell death. Loss of cell-surface Fas expression and failure of Fas (CD95)-dependent apoptotic death has been observed when cells develop drug resistance. The defect in apoptosis can be overcome by anti-cancer agents or experimental manipulation that induce Fas expression on the drug-resistant cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis*
  • Antimetabolites, Antineoplastic / pharmacology*
  • Apoptosis
  • B7-1 Antigen / biosynthesis*
  • B7-2 Antigen
  • Carcinogens / pharmacology
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drug Resistance
  • Immune System / drug effects*
  • Kinetics
  • Membrane Glycoproteins / biosynthesis*
  • Methotrexate / pharmacology
  • Mice
  • Staurosporine / pharmacology
  • Trimetrexate / pharmacology
  • fas Receptor / biosynthesis*

Substances

  • Antigens, CD
  • Antimetabolites, Antineoplastic
  • B7-1 Antigen
  • B7-2 Antigen
  • Carcinogens
  • Cd86 protein, mouse
  • Membrane Glycoproteins
  • fas Receptor
  • Staurosporine
  • Trimetrexate
  • Methotrexate