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

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.