Therapeutic monoclonal antibodies (mAb) have changed the landscape of cancer therapy. With advances in the understanding of tumour biology and its microenvironment, different categories of mAbs have been developed; a first category is directed against tumour cells themselves, a second one comprises antibodies blocking the formation of neo-vasculature that accompanies tumour development, and, during the last decades, a third new category of immunomodulatory antibodies that target immune cells in the tumour microenvironment rather than cancer cells has emerged. In this chapter, we outline the main mechanisms of action of the different anti-tumour antibodies. We discuss the notion that, rather than passive immunotherapy that solely induces tumour cell killing, mAbs have multifaceted effects on the tumour microenvironment and could, qualitatively and quantitatively, reshape the immune infiltrate. We also discuss bystander effects of mAbs on the tumour microenvironment that should be carefully considered for the design of new therapeutic strategies.
Keywords: Antibody-dependent cellular cytotoxicity; Antibody-dependent cellular phagocytosis; Bystander effects of monoclonal antibodies; Cancer therapy; Fab- and Fc-dependent mechanisms of action; Fc gamma receptors; IgG; Immune checkpoints; Immunotherapy; Innate immunity; Long-term adaptive immunity; Modulation of anti-tumour adaptive immunity; Monoclonal antibodies; Tumour microenvironment; Vaccinal effect.