Obesity-associated cancer: an immunological perspective

Abstract

Epidemiological studies have established an association between obesity, insulin resistance, type 2 diabetes and a number of cancer types. Research has focused predominantly on altered endocrine factors, growth factors and signalling pathways, with little known in man about the immune involvement in the relevant pathophysiological processes. Moreover, in an era of exciting new breakthroughs in cancer immunotherapy, there is also a need to study the safety and efficacy of immunotherapeutics in the complex setting of inflammatory-driven obesityassociated cancer. This review addresses key immune cell subsets underpinning obesityassociated inflammation and describes how such immune compartments might be targeted to prevent and treat obesity-associated cancer. We propose that the modulation, metabolism, migration and abundance of pro-and anti-inflammatory cells and tumour-specific T cells might be therapeutically altered to both restore immune balance, alleviating pathological inflammation, and to improve anti-tumour immune responses in obesity-associated cancer. Obesity: Cancer: Lymphocytes: Immunotherapeutics: InflammationThe burgeoning global health burden of obesity is of grave concern, affecting over half a billion adults worldwide, with approximately 3·5 million attributable deaths each year (1) . Despite national and international interventions to promote a healthy diet and lifestyle, recent reports predict that global obesity rates show no signs of abating, with predictions that half of all adults will be overweight or obese by 2030 (WHO). The worldwide prevalence of obesity almost doubled in the period 1980-2008. In 1980, 5 % of men and 8 % of women were obese and by 2008, these rates were 10 and 14 %, respectively. In many areas of the western world, the overweight phenotype is now the most prevalent body type. For example, in the USA in 2010 the prevalence of a BMI ≥ 25 was 69·2 %, with 35·9 % of people being obese (BMI ≥ 30) (2)

CCR1 antagonism attenuates T cell trafficking to omentum and liver in obesity‐associated cancer

“…Notwithstanding government campaigns promoting lifestyle interventions and laws and taxes to curb increasing obesity rates, millions of adults and children worldwide are obese and these numbers continue to grow, along with the incidence of obesity-associated disease. 1,3 The omentum and liver of obese individuals are sites of excessive inflammation, fuelled in part by an abundance of inflammatory T cells and macrophages. 5,6 The combination of functional T cell subsets recruited to a site are shaped by the expression of local chemokines and therefore blocking inflammatory T cell migration to these sites holds promise in models of inflammatory diseases, as exemplified for rheumatoid arthritis.…”

“…Global obesity rates have reached epidemic proportions and the associated health burden is a major concern in the western world 1 . Furthermore, recent reports estimate that half of the world's adult population will be overweight or obese by 2030 and the prevalence of obesity‐associated diseases, such as cancer and non‐alcoholic fatty liver disease (NAFLD) are set to continue to rise and create a major burden on health services 1 , 2 , 3 . Accordingly, in addition to prevention of obesity, improved understanding of the pathological inflammation which fuels obesity‐associated disease is urgently required.…”

The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance

“…Moreover, the modification of the immune environment (including the recruitment of pro-inflammatory macrophages) arising in AT during obesity is also probably very important in terms of cancer progression. Readers interested in these aspects could refer to recent reviews [ 22 , 23 ].…”

Innate Lymphocytes in Adipose Tissue Homeostasis and Their Alterations in Obesity and Colorectal Cancer

“…Obesity is associated with profound changes in AT infiltrates and systemic profiles of innate lymphocytes, contributing to the dysregulated soluble mediator release and to skewing the balance toward a pro-inflammatory status ( 8 ). In addition to act as major regulators of AT homeostasis, innate T cell populations actively contribute to the early defense against cancer ( 9 , 10 ).…”

“…The altered systemic and AT environment occurring in obesity not only increases the likelihood of tumor development/progression but also sets the basis for unfavorable responses to therapeutic regimens ( 9 , 10 ). Several studies suggest that, within the constitutively active pro-inflammatory AT microenvironment characterizing obesity, the bidirectional cross-talk between AT and cancer cells may play an important role ( 50 ).…”