Abstract
Cancer is one of the leading causes of morbidity and mortality worldwide. Traditional treatments include surgery, chemotherapy and radiation therapy, and more recently targeted therapies including immunotherapy are becoming routine care for some cancers. Immunotherapy aims to upregulate the patient’s own immune system, enabling it to destroy cancerous cells. Obesity is a metabolic disorder characterized by significant weight that is an important contributor to many different diseases, including cancers. Obesity impacts the immune system and causes, among other things, a state of chronic low-grade inflammation. This is hypothesized to impact the efficacy of the immunotherapies. This review discusses the effects of obesity on the immune system and cancer immunotherapy, including the current evidence on the effect of obesity on immune checkpoint blockade, something which currently published reviews on this topic have not delved into. Data from several studies show that even though obesity causes a state of chronic low-grade inflammation with reductions in effector immune populations, it has a beneficial effect on patient survival following anti-PD-1/PD-L1 and anti-CTLA-4 treatment. However, research in this field is just emerging and further work is needed to expand our understanding of which cancer patients are likely to benefit from immunotherapy.
Highlights
Cancer and ObesityCancer is a non-communicable disease brought about by changes within cells, resulting in their uncontrolled growth and division [1]
Obesity affects the immune system in a way that is relevant in both cancer progression and treatment, and the general hypothesis is that these changes will reduce the efficacy of immune-based treatments
Anti-Programmed Death (PD)-1/PD-L1 therapy, which inhibits this interaction and allows CD8+ T-cells to have increased ability to kill tumour cells, would be more efficacious (Figure 2). This theory is supported by the study by Kichenadasse et al, who found that the association between obesity and immune checkpoint blockade success was strongest in patients with a higher expression of PD-L1, while there was no difference in survival in patients with
Summary
Cancer is a non-communicable disease brought about by changes within cells, resulting in their uncontrolled growth and division [1] It is one of the leading causes of mortality worldwide, and most deaths attributed to cancer worldwide are from lung, breast, colorectal, stomach and liver cancers [2,3]. According to World Health Organisation estimates, in 2016, 39% of adults aged 18 years or older were found to be overweight and 13% were obese globally. The prevalence of these conditions has risen in both adults and children [2]. Obese (BMI > 35) as well as underweight (BMI < 18.5) patients have higher mortality rates following curative cancer resection surgery compared to normal weight and overweight patients [12]
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