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Miller et al. J Cancer Metastasis Treat 2019;5:68 Journal of Cancer
DOI: 10.20517/2394-4722.2019.001 Metastasis and Treatment

Review Open Access

The immunological regulation of cancer cachexia

and its therapeutic implications

Janice Miller , Barry J. A. Laird , Richard J. E. Skipworth 1
2
1
1 Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh EH16 4SA, UK.
2 Edinburgh Palliative and Supportive Care Group, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.

Correspondence to: Dr. Richard J. E. Skipworth, Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, 51 Little
France Crescent, Edinburgh EH16 4SA, UK. E-mail: richard.skipworth@nhslothian.scot.nhs.uk

How to cite this article: Miller J, Laird BJA, Skipworth RJE. The immunological regulation of cancer cachexia and its therapeutic
implications. J Cancer Metastasis Treat 2019;5:68. http://dx.doi.org/10.20517/2394-4722.2019.001

Received: 7 Apr 2019 First Decision: 1 July 2019 Revised: 11 Sep 2019 Accepted: 25 Sep 2019 Published: 30 Sep 2019

Science Editor: Bingliang Fang Copy Editor: Cai-Hong Wang Production Editor: Tian Zhang

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.

Keywords: Cancer cachexia, interleukins, macrophages, immunotherapy

INTRODUCTION
Cachexia is “a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without
loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive
© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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