Grafanaki Katerina, Maniatis Alexandros, Anastogianni Alexandra, Bania Angelina, Pasmatzi Efstathia, Stathopoulos Constantinos
Department of Dermatology-Venereology, School of Medicine, University of Patras, 26504 Patras, Greece.
Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece.
J Clin Med. 2025 Jun 12;14(12):4193. doi: 10.3390/jcm14124193.
: Melanoma, one of the most aggressive forms of skin cancer, has seen significant therapeutic advances with immune checkpoint inhibitors (ICIs). However, many patients fail to respond or develop resistance, creating the need for adjunct strategies. : The objective of this study is to critically evaluate how specific dietary patterns and nutrient-derived metabolites modulate melanoma metabolism and immunotherapy outcomes, emphasizing translational implications. : We performed an integrative review of preclinical and clinical studies investigating dietary interventions in melanoma models and ICI-treated patients. Mechanistic insights were extracted from studies on nutrient transport, immunometabolism, and microbiome-immune interactions, including data from ongoing nutritional clinical trials. : Diets rich in fermentable fibers, plant polyphenols, and unsaturated lipids, such as Mediterranean and ketogenic diets, seem to contribute to the reprogramming of tumor metabolism and enhance CD8+ T-cell activity. Fasting-mimicking and methionine-restricted diets modulate T-cell fitness and tumor vulnerability via nutrient stress sensors (e.g., UPR, mTOR). High fiber intake correlates with favorable gut microbiota and improved ICI efficacy, while excess protein, methionine, or refined carbohydrates impair immune surveillance via lactate accumulation and immunosuppressive myeloid recruitment. Several dietary molecules act as network-level modulators of host and microbial proteins, with parallels to known drug scaffolds. : Integrating dietary interventions into melanoma immunotherapy can significantly influence metabolic reprogramming by targeting metabolic vulnerabilities and reshaping the tumor-immune-microbiome axis. When combined with AI-driven nutrient-protein interaction mapping, this approach offers a precision nutrition paradigm that supports both physicians and patients, emerging as a novel layer to enhance and consolidate existing therapeutic strategies.
黑色素瘤是皮肤癌中侵袭性最强的类型之一，免疫检查点抑制剂（ICI）使其治疗取得了显著进展。然而，许多患者无反应或产生耐药性，因此需要辅助策略。
本研究的目的是严格评估特定饮食模式和营养衍生代谢物如何调节黑色素瘤代谢和免疫治疗结果，并强调其转化意义。
我们对临床前和临床研究进行了综合评价，这些研究调查了黑色素瘤模型和接受ICI治疗的患者的饮食干预情况。从关于营养物质转运、免疫代谢和微生物群 - 免疫相互作用的研究中提取了机制见解，包括来自正在进行的营养临床试验的数据。
富含可发酵纤维、植物多酚和不饱和脂质的饮食，如地中海饮食和生酮饮食，似乎有助于肿瘤代谢的重编程并增强CD8 + T细胞活性。模拟禁食和限制蛋氨酸的饮食通过营养应激传感器（如未折叠蛋白反应、雷帕霉素靶蛋白）调节T细胞适应性和肿瘤易感性。高纤维摄入与良好的肠道微生物群和改善的ICI疗效相关，而过量的蛋白质、蛋氨酸或精制碳水化合物会通过乳酸积累和免疫抑制性髓系细胞募集损害免疫监视。几种饮食分子可作为宿主和微生物蛋白的网络水平调节剂，与已知药物支架类似。
将饮食干预整合到黑色素瘤免疫治疗中可以通过靶向代谢弱点和重塑肿瘤 - 免疫 - 微生物群轴来显著影响代谢重编程。当与人工智能驱动的营养 - 蛋白质相互作用图谱相结合时，这种方法提供了一种精准营养模式，可为医生和患者提供支持，成为增强和巩固现有治疗策略的新层面。
