Cysteine cathepsins: regulators of antitumour immune response

Abstract

Cysteine cathepsins are lysosomal cysteine proteases that are involved in a number of important biological processes, including intracellular protein turnover, propeptide and hormone processing, apoptosis, bone remodelling and reproduction. In cancer, the cathepsins have been linked to extracellular matrix remodelling and to the promotion of tumour cell motility, invasion, angiogenesis and metastasis, resulting in poor outcome of cancer patients; however, cysteine cathepsins are also involved at different levels of the innate and adaptive immune responses. Their best known role in this aspect is their contribution to major histocompatibility complex class II antigen presentation, the processing of progranzymes into proteolytically active forms, cytotoxic lymphocyte self-protection, cytokine and growth factor degradation and, finally, the induction of cytokine expression and modulation of integrin function. This review is focused on the role of cysteine cathepsins in the antitumour immune response and the evaluation of their pro- and anticancer behaviours during the regulation of these processes.