Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice

Science. 1992 Dec 11;258(5089):1795-8. doi: 10.1126/science.1465616.

Abstract

Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8+ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-alpha and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3 gamma and completely lacked CD3 zeta, which was replaced by the Fc epsilon gamma-chain. Expression of the tyrosine kinases p56lck and p59fyn was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts.

Publication types

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

MeSH terms

  • Animals
  • CD3 Complex / metabolism
  • CD8 Antigens / analysis
  • Calcium / metabolism
  • Colonic Neoplasms / immunology*
  • Cytotoxicity, Immunologic*
  • Granzymes
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Macromolecular Substances
  • Mice
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fyn
  • Receptors, Antigen, T-Cell / isolation & purification
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, IgG / metabolism
  • Serine Endopeptidases / biosynthesis
  • Serine Endopeptidases / genetics
  • Signal Transduction*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • CD3 Complex
  • CD8 Antigens
  • Macromolecular Substances
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, IgG
  • Tumor Necrosis Factor-alpha
  • Protein-Tyrosine Kinases
  • Fyn protein, mouse
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Proto-Oncogene Proteins c-fyn
  • Granzymes
  • Gzmb protein, mouse
  • Serine Endopeptidases
  • Calcium