TY - JOUR
T1 - Cellular requirements for the monoclonal antibody-mediated eradication of an established solid tumor
AU - Dyall, Ruben
AU - Vasovic, Ljiljana V.
AU - Clynes, Raphael A.
AU - Nikolić-Žugić, Janko
PY - 1999
Y1 - 1999
N2 - 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 Fcγ receptors (FcγR), as it failed to occur in mice depleted of CD8 cells, or mice genetically deficient in FcγRI/III (γ(-/-) mice). Using adoptive transfer, we now show that the FcγR+ 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+ FcγR+ 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 effecters essential for the mAb-mediated tumor regression, and suggest that FcγR-activated macrophages induced an expansion of tumor-eliminating CTL in situ.
AB - 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 Fcγ receptors (FcγR), as it failed to occur in mice depleted of CD8 cells, or mice genetically deficient in FcγRI/III (γ(-/-) mice). Using adoptive transfer, we now show that the FcγR+ 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+ FcγR+ 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 effecters essential for the mAb-mediated tumor regression, and suggest that FcγR-activated macrophages induced an expansion of tumor-eliminating CTL in situ.
KW - Antibody
KW - CD8 cell
KW - FcγR
KW - Macrophage
KW - Tumor regression
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U2 - 10.1002/(SICI)1521-4141(199901)29:01<30::AID-IMMU30>3.0.CO;2-D
DO - 10.1002/(SICI)1521-4141(199901)29:01<30::AID-IMMU30>3.0.CO;2-D
M3 - Article
C2 - 9933083
AN - SCOPUS:0032895775
SN - 0014-2980
VL - 29
SP - 30
EP - 37
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 1
ER -