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Page 8 of 11 Miller et al. J Cancer Metastasis Treat 2019;5:68 I http://dx.doi.org/10.20517/2394-4722.2019.001

These studies therefore raise the possibility that immunotherapies could represent effective anti-cachexia
agents but that synchronous multimodal and nutritional anti-cancer treatments may be required to
establish or enhance their overall effectiveness.

A key consideration in using immunotherapy may be the inflammatory status of the host. It has been
demonstrated that the host inflammatory status influences the efficacy of therapy with inflamed patients
[81]
most likely to benefit from therapies with an anti-inflammatory mode of action . Similar to the call to
[82]
“stage the tumor, stage the host” it is now key that treatment stratification is based on the inflammatory
status of the patient and this is now being used as a mandatory measure in clinical trials in some tumour
[83]
groups . It is clear that whilst immunotherapies as a treatment for cancer cachexia, there is a necessity to
ensure patients who receive these are those who are most likely to benefit.

CONCLUSION
The pathogenesis of cancer cachexia is highly dependent on the patient’s immune response. The interplay
between inflammatory cytokines (such as TNF-α, IFNg and interleukins) and pro-cachectic factors
contributes to the complex aetiology. These cytokines are produced by the host in response to the tumour,
as well as by the tumour itself. Many treatments have tried to regulate the immune response in cachexia
but have largely been unsuccessful, perhaps in part due to the multifactorial nature of cachexia, and
the observed heterogeneity of patient factors. Large-scale clinical studies are needed to prove whether
neutralisation of deleterious cytokines or direct receptor antagonism in combinatorial treatment regimens
is an effective therapeutic approach to improve patient outcomes or to reverse muscle loss in cancer
cachexia.

DECLARATIONS
Authors’ contributions

Drafted the manuscript: MillerJ

Critically revised the manuscript and gave final approval for the version to be published: Laird BJA,

SkipworthRJE
Availability of data and materials
Not applicable.

Financial support and sponsorship
Miller J is supported by Cancer Research UK and the Royal College of Surgeons of Edinburgh. Skipworth

RJE is supported by an NHS Research for Scotland (NRS) funded post.

Conflicts of interest
The authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.