Cellular requirements for the monoclonal antibody-mediated eradication of an established solid tumor

Eur J Immunol. 1999 Jan;29(1):30-7. doi: 10.1002/(SICI)1521-4141(199901)29:01<30::AID-IMMU30>3.0.CO;2-D.


Following subcutaneous implantation, the murine lymphoma E.G7 [a variant of EL-4, transfected with the chicken ovalbumin (OVA) gene] up-regulates the CD4 molecule. We previously showed that the administration of an anti-CD4 monoclonal antibody (mAb) to EG.7-bearing mice leads to a rapid and complete regression of large established tumors. This tumor regression was shown to require both CD8+ cells and functional Fcgamma receptors (FcgammaR), as it failed to occur in mice depleted of CD8 cells, or mice genetically deficient in FcgammaI/III (gamma-/-mice). Using adoptive transfer, we now show that the FcgammaR+ cells required for this regression are the CD11b+ (phagocytic) cells. Furthermore, experiments using peptide tolerization demonstrated that the critical CD8 CTL population in this model is tumor specific. Analysis of tumors at various stages of regression revealed a massive CD11b+FcgammaR+ and a marginal CD8 infiltration. In the presence of the CTL determinant OVA-8 on tumor cells and of the antitumor mAb, this CD8 infiltration became remarkable, and correlated with tumor regression. These results identify the specific cellular effectors essential for the mAb-mediated tumor regression, and suggest that FcgammaR-activated macrophages induced an expansion of tumor-eliminating CTL in situ.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • CD4 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Chickens
  • Hematopoietic Stem Cells / immunology
  • Kinetics
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Lymphoma / immunology*
  • Lymphoma / pathology
  • Lymphoma / therapy*
  • Macrophage-1 Antigen / metabolism
  • Mice
  • Mice, Knockout
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • Transfection


  • Antibodies, Monoclonal
  • CD4 Antigens
  • Macrophage-1 Antigen
  • Receptors, IgG
  • Ovalbumin