The immunological regulation of cancer cachexia and its therapeutic implications

Abstract

Cachexia affects the majority of patients with advanced cancer. It leads to poor surgical and oncological outcomes, and negatively affects quality of life. It has long been reported that components of the host immune system, including pro-inflammatory cytokines such as IL-1α, IL-6, TNF-α and INF-g, participate in the syndrome of cachexia. Yet therapeutic targeting of these pro-inflammatory factors has not yielded meaningful improvements in cachexia management. More recently, the impact of immune cells in the tumour mass (tumour-associated macrophages) and host circulation (myeloid suppressor cells) has garnered much interest with regards to their role in immune tolerance in cancer. However, their role in the generation of systemic inflammation and cancer cachexia is underexplored and outstanding questions remain. This review summarises the key mediators and targets of immune dysfunction in cancer cachexia. Here we describe the host response including skeletal muscle wasting; highlight the current knowledge gap areas; and report the results of previously trialled immunotherapies. A greater understanding of complex interaction between the tumour, immune system and peripheral tissues in the genesis and maintenance of cancer cachexia is a key step in n identifying future therapeutic targets.