Zhang Chunye, Zhu Keyao, Liu Jiazheng, Yang Ming
Bond Life Sciences Center, University of Missouri, Columbia, MO 65212, USA.
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau 999078, China.
Diseases. 2025 Aug 21;13(8):271. doi: 10.3390/diseases13080271.
Cancer is a leading cause of death worldwide, causing about 10 million deaths annually. Obesity contributes to cancer progression by inducing chronic inflammation, immunosuppressive microenvironment, metabolic dysfunction, and therapeutic resistance. Accumulating evidence shows that obesity can advance the infiltration of immunosuppressive cells and ameliorate the function and cytotoxicity of tumor-killing cells such as natural killer cells, natural killer T cells, macrophages, and CD8 T cells in cancer patients, resulting in cancer progression. Understanding the molecular signaling pathways involved in obesity-induced immunosuppression and cancer cell proliferation enables us to screen new biomarkers for cancer early diagnosis and improve anti-tumor therapeutic efficacy in obese patients with cancer. In this review, we first review the molecular mechanisms by which obesity induces the immunosuppressive landscape in the tumor microenvironment and some key obesity-associated factors causing immunotherapeutic suppression and metabolic dysfunction. Then, the application of natural products in the treatment of obesity and obesity-associated cancers is summarized. In addition, we discuss the contradictory functions of obesity in cancer risk and treatment outcome. The potent roles of precision medicine and artificial intelligence in the management of obesity-related cancers are highlighted.
癌症是全球主要的死亡原因之一,每年导致约1000万人死亡。肥胖通过诱导慢性炎症、免疫抑制微环境、代谢功能障碍和治疗抵抗促进癌症进展。越来越多的证据表明,肥胖会促进免疫抑制细胞的浸润,并削弱癌症患者体内自然杀伤细胞、自然杀伤T细胞、巨噬细胞和CD8 T细胞等杀伤肿瘤细胞的功能和细胞毒性,从而导致癌症进展。了解肥胖诱导免疫抑制和癌细胞增殖所涉及的分子信号通路,有助于我们筛选用于癌症早期诊断的新生物标志物,并提高肥胖癌症患者的抗肿瘤治疗效果。在本综述中,我们首先回顾肥胖诱导肿瘤微环境中免疫抑制格局的分子机制,以及一些导致免疫治疗抑制和代谢功能障碍的关键肥胖相关因素。然后,总结天然产物在肥胖及肥胖相关癌症治疗中的应用。此外,我们还讨论了肥胖在癌症风险和治疗结果中的矛盾作用。强调了精准医学和人工智能在肥胖相关癌症管理中的重要作用。