Natural killer cell therapy: A new frontier for obesity-associated cancer.

Natural killer (NK) cell infiltration of solid tumours is associated with better outcomes, placing augmentation of NK cell abundance in tumours as an attractive immunotherapeutic approach. The unique ability of NK cells to target cancer cells without antigen specificity increases their versatility and applicability as an immunotherapeutic tool. However, successful utilisation of NK cell-based therapies in solid tumours is still at an early stage. Obesity has become a global health epidemic, and the prevalence of obesity-associated cancers has significantly increased. Obesity-associated malignancies provide a unique challenge for the successful application of cell-based immunotherapies including NK cell-based therapies because significant numbers of NK and T cells are recruited to the visceral adipose tissue at the expense of successful tumour infiltration and eradication. As such, immunotherapy efficacy has been disappointing for obesity-associated malignancies such as oesophageal and gastric adenocarcinoma. Therefore, immunotherapies for obesity-associated cancers warrant our further attention. Indeed, it is becoming ever more obvious that more innovative approaches are needed to re-invigorate anti-tumour immunity and overcome immune exclusion in such tumours. In this review, we briefly summarise the dysfunctionality of NK cells in obesity-associated cancer. We outline the NK cell-based immunotherapeutic approaches which hold promise as effective treatments in this disease space, including CAR-NK cells. Furthermore, we suggest future avenues which possess the potential to transform immunotherapy and specifically NK cell therapy efficacy for obesity-associated cancer.