Cervical cancer cells induce apoptosis of cytotoxic T lymphocytes

J Immunother. 2000 Jan;23(1):67-74. doi: 10.1097/00002371-200001000-00009.

Abstract

The goal of immunotherapy is to eliminate tumors by generating tumor-specific cytotoxic T lymphocytes (CTLs) in patients or by adoptively transferring ex vivo-activated CTLs into patients. Clinical trials have shown that tumor-specific CTLs often disappear before tumors are completely eliminated. In this study, the authors show that CTLs specific for cervical tumor cells undergo apoptosis after they are co-cultured with cervical tumor cells. The established cervical tumor cell lines and cervical cancer tissues express CD95 (Fas/Apo-1) ligand. The tumor cell-induced T-cell apoptosis can be blocked by an inhibitory anti-CD95 (APO-1/Fas) antibody, indicating that tumor cells induce apoptosis of CTLs through CD95-CD95 ligand interaction. Addition of interleukin-2 (IL-2) and IL-7 into the culture rescues the CTL from tumor cell-induced apoptosis. The rescued T cells retain their full antitumor cytotoxicity. These data suggest that human cervical tumor cells might actively down-regulate a cellular immune response by inducing apoptosis of specific T cells during immunotherapy. Local use of IL-2 and IL-7 as adjuvants may promote survival of the CTL and, thus, enhance the efficacy of immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Coculture Techniques
  • Fas Ligand Protein
  • Female
  • HeLa Cells
  • Humans
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology
  • Interleukin-7 / immunology
  • Interleukin-7 / pharmacology
  • Jurkat Cells
  • Ligands
  • Lymphocyte Activation
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / immunology*
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / blood
  • Uterine Cervical Neoplasms / immunology*
  • fas Receptor / immunology*

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-2
  • Interleukin-7
  • Ligands
  • Membrane Glycoproteins
  • fas Receptor