There is strong epidemiological data linking obesity to an increased risk of various cancers. It is associated with immune dysregulation and chronic low grade inflammation, however little is known about its impact on anti-tumour immunity. Whether childhood obesity is an independent risk factor for future malignancy is not fully established. We hypothesized that alterations in key immune anti-tumour mechanisms begin prior to adulthood in paediatric obesity.
MicroRNA-34a (miR-34a) is a transcriptional target of p53 that is down-regulated in some cancer cell lines. Natural killer cells and cytotoxic T cells are vital to tumour rejection. Invariant natural killer T cells are important bridging cells between the innate and adaptive immune system.
Peripheral blood mononuclear cells were isolated from 61 patients aged 618 years. The expression of microRNA 34a (miR34a), a target for tumour suppressor gene p53 was quantitatively measured. Cytotoxicity assays determining natural killer (NK) cell activity and immunophenotyping were performed.
|Parameter||Obese (n=40)||Non-obese (n=21)||P value|
|CD8 cytotoxic T cells (%CD3+T cells)||25.3±7.1||30.3±6.6||0.03|
|Invariant natural killer T cell (%CD3+T cells) iNKT||0.32±0.03||0.54±0.02||<0.001|
|NK cytotoxicity (K562 tumour cell death)||201±88||615±122||0.01|
|miR 34a expression (relative quantification)||0.72±0.1||1.8±0.2||<0.001|
|Data expressed as mean±S.D. P values calculated using independent-samples t-test.|
The age and BMI Z-score of obese participants were 12.9±3.0 years and 3.3±0.4 respectively and non-obese participants were 12.2±2.9 years and 0.4±0.9.
A reduction in cytotoxic cell capacity and targets of potent tumour suppressor gene expression occurs from an early age in obese children and may be contributing to future cancer risk in this population.