Excess Body Fat and Liver Cancer Immunotherapy Resistance: The Role of Diet in Improved Outcomes

Recent research highlights a significant link between excess fat accumulation and resistance to immunotherapy treatments in liver cancer patients. A collaborative study by the University of Hong Kong's LKS Faculty of Medicine and Peking University has revealed that fat within liver tumors can modify immune cells, leading to immune evasion and diminished treatment effectiveness. Specifically, fatty liver conditions foster a unique population of neutrophils capable of producing tumor-supporting factors that enable cancer cells to escape immune attacks.

The study observed that by depleting these neutrophils or blocking their development, the immune system's response to immunotherapy could be restored, offering a promising strategy to improve treatment outcomes for resistant cases. The findings also emphasize that unhealthy lifestyles, including high-fat diets and physical inactivity, contribute to abnormal fat buildup, which exacerbates the problem.

Liver cancer remains a major health concern, especially in Hong Kong, where it ranks as the fifth leading cause of cancer-related deaths. Despite advancements such as immune checkpoint blockade (ICB) therapy, only about 30% of liver cancer patients benefit, with many experiencing limited survival gains. A particularly aggressive subtype, MASH-HCC, is notably resistant to immunotherapy, mainly due to excessive fat deposits associated with metabolic dysfunction.

These insights underscore the importance of healthier dietary habits and lifestyle interventions to prevent liver fat accumulation and potentially enhance the efficacy of immunotherapies. Professor Heidi Ling Guang-sheng from HKUMed emphasizes that adopting a healthy diet and lifestyle is crucial not only for liver protection but also for improving treatment responses.

This research paves the way for new combination therapies targeting neutrophil activity, offering hope for better management of resistant liver cancer subtypes. Ongoing studies aim to develop strategies that could make immunotherapy more effective for all patients, particularly those with fatty liver conditions.