Clynes R, Takechi Y, Moroi Y, Houghton A, Ravetch J V
Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY, USA.
Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):652-6. doi: 10.1073/pnas.95.2.652.
Effective tumor immunity requires recognition of tumor cells coupled with the activation of host effector responses. Fc receptor (FcR) gamma-/- mice, which lack the activating Fc gamma R types I and III, did not demonstrate protective tumor immunity in models of passive and active immunization against a relevant tumor differentiation antigen, the brown locus protein gp75. In wild-type mice, passive immunization with mAb against gp75 or active immunization against gp75 prevented the development of lung metastases. This protective response was completely abolished in FcR gamma-deficient mice. Immune responses were intact in gamma-/- mice because IgG titers against gp75 develop normally in gamma-/- mice immunized with gp75. However, uncoupling of the Fc gamma R effector pathway from antibody recognition of tumor antigens resulted in a loss of protection against tumor challenge. These data demonstrate an unexpected and critical role for FcRs in mediating tumor cytotoxicity in vivo and suggest that enhancement of Fc gamma R-mediated antibody-dependent cellular cytotoxicity by inflammatory cells is a key step in the development of effective tumor immunotherapeutics.
有效的肿瘤免疫需要识别肿瘤细胞并激活宿主效应反应。缺乏激活型FcγR I型和III型的Fc受体（FcR）γ-/-小鼠，在针对相关肿瘤分化抗原棕色位点蛋白gp75的被动和主动免疫模型中未表现出保护性肿瘤免疫。在野生型小鼠中，用抗gp75单克隆抗体进行被动免疫或针对gp75进行主动免疫可预防肺转移的发生。这种保护反应在FcRγ缺陷小鼠中完全消失。γ-/-小鼠的免疫反应是完整的，因为在用gp75免疫的γ-/-小鼠中，针对gp75的IgG滴度正常产生。然而，FcγR效应途径与肿瘤抗原的抗体识别脱钩导致对肿瘤攻击的保护作用丧失。这些数据证明了FcR在体内介导肿瘤细胞毒性方面出乎意料的关键作用，并表明炎症细胞增强FcγR介导的抗体依赖性细胞毒性是有效肿瘤免疫治疗发展的关键步骤。
