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Updated: Sep 30, 2025
Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Natural killer cell therapy: A new frontier for obesity-associated cancer
Eimear Mylod1, Joanne Lysaght1, Melissa J Conroy2
1Cancer Immunology and Immunotherapy Group, Department of Surgery, Trinity Translational Medicine Institute and Trinity St. James's Cancer Institute, St. James's Hospital, Trinity College Dublin, Dublin, 8, Ireland.
Abstract:
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.
Insights
Natural killer (NK) cell therapy shows promise for obesity-associated cancers, but obesity hinders effective tumor infiltration. Innovative strategies are needed to overcome immune challenges and improve NK cell immunotherapy efficacy.
Area of Science:
- Immunology
- Oncology
- Metabolic Diseases
Background:
- Natural killer (NK) cell infiltration in solid tumors correlates with improved patient outcomes.
- Obesity is a growing global health concern, increasingly linked to various cancers, posing unique challenges for immunotherapies.
- Obesity-associated cancers, like esophageal and gastric adenocarcinoma, show disappointing responses to current immunotherapies due to NK and T cell sequestration in visceral adipose tissue.
Purpose of the Study:
- To review the dysfunctionality of NK cells in the context of obesity-associated cancers.
- To explore promising NK cell-based immunotherapeutic strategies, including CAR-NK cells, for these malignancies.
- To identify future research directions for enhancing NK cell therapy efficacy in obesity-associated cancers.
Main Methods:
- Review of existing literature on NK cell function, obesity, and cancer immunology.
- Analysis of challenges posed by obesity to cell-based immunotherapies.
- Discussion of emerging NK cell-based therapeutic approaches.
Main Results:
- Obesity impairs NK cell function and tumor infiltration, compromising anti-tumor immunity.
- CAR-NK cells and other novel strategies demonstrate potential for overcoming obesity-induced immune suppression.
- Significant numbers of immune cells are recruited to visceral adipose tissue, diverting them from tumor sites.
Conclusions:
- NK cell-based immunotherapies offer a promising avenue for treating obesity-associated cancers.
- Overcoming immune exclusion and reinvigorating anti-tumor immunity are critical for therapeutic success.
- Further research into innovative approaches is essential to optimize NK cell therapy for patients with obesity-related malignancies.
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