Department of Internal Medicine, 251 Airforce General Hospital, Kanellopoulou 3, 11525, Athens, Greece.
Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou str, 10676, Athens, Greece.
Semin Cancer Biol. 2021 Aug;73:356-376. doi: 10.1016/j.semcancer.2021.05.008. Epub 2021 May 11.
Immunotherapy has recently emerged as a promising treatment option for many patients, revolutionizing the established therapeutic approach against cancer. Immune checkpoints inhibitors (ICIs) have demonstrated clinical activity in a wide spectrum of malignancies; however, only a minority of patients exhibit durable responses. This response heterogeneity may be partly attributed to host related factors, such as body mass index (BMI), diet and gut microbiome, that have recently emerged as strong influences in ICI responsiveness. Obesity not only directly impacts on cancer promotion but also on the immune homeostasis and the elimination, equilibrium, and escape phases of immune-editing. Paradoxically, emerging clinical data indicate that obese patients are benefited from ICI therapy when compared to normal BMI cancer patients. Interestingly, strong evidence supports the role of the microbiome in cancer immunotherapy, with several recent animal, translational/hybrid and clinical studies demonstrating its influence in the response to ICIs across several malignancies. Noteworthy, nutrition, through its well-established links to obesity, microbiome composition and oncogenicity, may contribute towards leveraging its effects in favor of cancer patients alongside with gold standard treatments. The aim of this review is to delineate the associations of ICIs with obesity, host microbiome and nutrition, and to explore how these factors can be effectively leveraged in enhancing the effectiveness of immunotherapy. More specific aims include the determination of how patients with obesity are differentially affected by ICI therapy; how the host microbiome affects response to ICIs; and how the microbiome itself is modulated by obesity and nutrition. In conclusion, immunometabolism, microbiome and nutrition research present the potential to offer unique tools in unleashing ICIs full potential; providing host-derived, actionable, modifiable targets directly associated with therapeutic outcomes that can be efficiently leveraged. Future efforts, provided that they adhere to robustness of methodology, can facilitate transferring these findings, from bench to bedside.
免疫疗法最近成为许多患者有希望的治疗选择，彻底改变了癌症的既定治疗方法。免疫检查点抑制剂（ICI）在广泛的恶性肿瘤中表现出临床活性；然而，只有少数患者表现出持久的反应。这种反应异质性可能部分归因于宿主相关因素，例如体重指数（BMI）、饮食和肠道微生物组，这些因素最近被认为是 ICI 反应性的强烈影响因素。肥胖不仅直接影响癌症的发生，还影响免疫平衡以及免疫编辑的消除、平衡和逃逸阶段。矛盾的是，新兴的临床数据表明，与正常 BMI 的癌症患者相比，肥胖患者从 ICI 治疗中获益。有趣的是，强有力的证据支持微生物组在癌症免疫治疗中的作用，最近的一些动物、转化/混合和临床研究表明，它在几种恶性肿瘤对 ICI 的反应中发挥作用。值得注意的是，营养通过其与肥胖、微生物组组成和致癌性的明确联系，可能有助于在与金标准治疗一起利用其对癌症患者的影响。本综述的目的是描绘 ICI 与肥胖、宿主微生物组和营养之间的关联，并探讨如何有效地利用这些因素来增强免疫疗法的效果。更具体的目标包括确定肥胖患者如何受到 ICI 治疗的不同影响；宿主微生物组如何影响对 ICI 的反应；以及微生物组本身如何被肥胖和营养调节。总之，免疫代谢、微生物组和营养研究有可能提供独特的工具，充分发挥 ICI 的潜力；提供与治疗结果直接相关的、可操作的、可改变的宿主来源的靶向，这些靶向可以有效地加以利用。未来的努力，如果它们符合方法学的稳健性，将有助于将这些发现从实验室转移到临床。
