Direct and indirect engagement of dendritic cell function by antibodies developed for cancer therapy.

Abstract

Dendritic cells (DC) are crucial for the priming of T cells and thereby influence adaptive immune responses. Hence, they also represent important players in shaping anti-tumour immune responses. Cancer immunotherapy has been driven over many years by the aim to harness the T-cell stimulatory activity of these crucial antigen-presenting cells (APC). Efficient antigen delivery alone is not sufficient for full engagement of the T-cell stimulatory activity of DC and the inclusion of adjuvants triggering appropriate DC activation is essential to ensure effective anti-tumour immunity induction. While the direct engagement of DC function is a powerful tool for tumour immunotherapy, many therapeutic antibodies, such as antibodies directed against tumour-associated antigens (TAA) and immune checkpoint inhibitors (ICI) have been shown to engage DC function indirectly. The induction of anti-tumour immune responses by TAA-targeting and immune checkpoint inhibitory antibodies is thought to be integral to their therapeutic efficacy. Here, we provide an overview of the immunotherapeutic antibodies in the context of cancer immunotherapy, that has been demonstrated to directly or indirectly engage DC and discuss the current understanding of the functional mechanisms underlying anti-tumour immunity induction by these antibody therapies. In the future, the combination of therapeutic strategies that engage DC function directly and/or indirectly with strategies that allow tumour infiltrating immune effector cells to exert their anti-tumour activity in the tumour microenvironment (TME) may be key for the successful treatment of cancer patients currently not responding to immunotherapeutic antibody treatment.