Cassard Lydie, Cohen-Solal Joël, Camilleri-Broët Sophie, Fournier Emilie, Fridman Wolf Herman, Sautès-Fridman Catherine
INSERM UMRs255, Université Paris 5 René Descartes, Université Paris 6 Pierre et Marie Curie, Centre de Recherches des Cordeliers, 15 rue de L’Ecole de Médecine, 75270, Paris Cedex 06, France,
Springer Semin Immunopathol. 2006 Dec;28(4):321-8. doi: 10.1007/s00281-006-0058-8. Epub 2006 Nov 10.
FcgammaRs are a family of heterogeneous molecules that play opposite roles in immune response and control the effector functions of IgG antibodies. In many cancers, IgG antibodies are produced that recognize cancer cells, form immune complexes and therefore, activate FcgammaR. The therapeutic efficacy of monoclonal IgG antibodies against hematopoietic and epithelial tumors also argue for an important role of IgG antibodies in anti-tumor defenses. Since the 1980s, a series of lines of evidence in experimental models and in humans strongly suggest that FcgammaR are involved in the therapeutic activity of monoclonal IgG antibodies by activating the cytotoxic activity of FcgammaR-positive cells such as NK cells, monocytes, macrophages and neutrophils and by increasing antigen presentation by dendritic cells. Since many cell types co-express activating and inhibitory FcgammaR, the FcgammaR-dependent effector functions of IgG anti-tumor antibodies are counterbalanced by the inhibitory FcgammaRIIB. In addition, some tumor cells express FcgammaR either constitutively, such as B cell lymphomas or ectopically, such as 40% of human metastatic melanoma. The tumor FcgammaR isoform is preferentially FcgammaRIIB, which is functional at least in human metastatic melanoma. This review summarizes these data and discusses how FcgammaRIIB expression may influence the anti-tumor immune reaction and how beneficial or deleterious this expression could be for the efficiency of therapeutics based on monoclonal anti-tumor antibodies.
Fcγ受体是一类异质性分子，在免疫反应中发挥相反作用，并控制IgG抗体的效应功能。在许多癌症中，会产生识别癌细胞的IgG抗体，形成免疫复合物，从而激活Fcγ受体。单克隆IgG抗体对造血系统肿瘤和上皮性肿瘤的治疗效果也表明IgG抗体在抗肿瘤防御中发挥重要作用。自20世纪80年代以来，实验模型和人体中的一系列证据有力地表明，Fcγ受体通过激活Fcγ受体阳性细胞（如自然杀伤细胞、单核细胞、巨噬细胞和中性粒细胞）的细胞毒活性以及增加树突状细胞的抗原呈递，参与单克隆IgG抗体的治疗活性。由于许多细胞类型共表达激活型和抑制型Fcγ受体，IgG抗肿瘤抗体的Fcγ受体依赖性效应功能会被抑制性FcγRIIB所抵消。此外，一些肿瘤细胞要么组成性表达Fcγ受体，如B细胞淋巴瘤，要么异位表达，如40%的人类转移性黑色素瘤。肿瘤Fcγ受体亚型优先为FcγRIIB，其至少在人类转移性黑色素瘤中具有功能。本综述总结了这些数据，并讨论了FcγRIIB的表达如何影响抗肿瘤免疫反应，以及这种表达对基于单克隆抗肿瘤抗体的治疗效果可能是有益还是有害。
