Figure 1:

(A) Schematic representing antibody structure with heavy and light chains, and Fab, hinge, and Fc regions. (B) Heavy chain constant regions of different isotype are labelled in: light blue (IgD), yellow (IgG), blue (IgE), pink (IgA), red (IgM); IgM and IgA J chain is in blue. (C) Antibody-mediated anti-tumour or pro-tumour effector functions. Antibodies can exert several anti-tumour effector functions: mediating ADCC, ADCP, and CDC. Antibodies engaged with FcRs on immune effector cells and bound to tumour-derived antigens to form immune complexes, can (a) repolarize immune cells such as NK cells and pro-tumour macrophages into pro-inflammatory, anti-tumour phenotypes and (b) facilitate antigen internalization, processing, and presentation to activate T cells. Antibodies can also exert direct cell killing, via antigen neutralization and blocking of downstream signalling, resulting in block of tumour growth and induction of apoptosis. Some IgG subclasses, such as IgG4, can exert pro-tumour functions. IgG4 has poor capacity to fix complement and lower ability to bind activating FcγRs and therefore lower ability to trigger effector functions compared to IgG1, and relatively high affinity for the inhibitory receptor FcγRIIb, resulting in negative immune effector cell activating signals, potentially blocking IgG1 mediated effector functions. See online supplementary material for a colour version of this figure.