Gamrath Lone, Pedersen Tobias Bruun, Møller Martin Vad, Volmer Lone Marie, Holst-Christensen Linda, Vestermark Lene Weber, Donskov Frede
Department of Oncology, University Hospital of Southern Denmark, Finsensgade 35, Esbjerg, 6700, Denmark.
Department of Clinical Diagnostics, University Hospital of Southern Denmark, Esbjerg, Denmark.
Curr Oncol Rep. 2025 Jan;27(1):45-58. doi: 10.1007/s11912-024-01622-6. Epub 2025 Jan 3.
The advent of checkpoint immunotherapy has dramatically changed the outcomes for patients with cancer. However, a considerable number of patients have little or no response to therapy. We review recent findings on the connection between the gut microbiota and the immune system, exploring whether this link could enhance the effectiveness of immunotherapy.
Clinical studies have reported specific types of bacteria in larger quantities at baseline in responders than in non-responders, especially Akkermansia mucinifila, Ruminococcaceae, Faecalibacterium, and Lachnospiraceae. Following the consumption of a high-fiber diet, bacteria in the gut ferment dietary fiber to short-chain fatty acids (SCFAs), like acetate, propionate, and butyrate. Some of the SCFAs nurture intestinal epithelial cells, and some enter the bloodstream. Here SCFAs can activate DC8 + cytotoxic T-cells to induce cancer cell death. High fiber intake in the diet was associated with a reduced risk of progression or death during checkpoint immunotherapy. Recent findings demonstrate that high-fiber plant-based diets such as the Mediterranean Diet positively influence the gut microbiota whereas antibiotics and proton pump inhibitors can negatively influence outcomes of cancer immunotherapy by changing the gut microbiota. This narrative review provides evidence of an association between types of bacteria and their metabolites and favorable responses to checkpoint immunotherapy. Prospective clinical trials are needed to determine if diet interventions can improve treatment outcomes.
检查点免疫疗法的出现极大地改变了癌症患者的治疗结果。然而,相当数量的患者对治疗反应甚微或没有反应。我们回顾了关于肠道微生物群与免疫系统之间联系的最新研究结果,探讨这种联系是否可以提高免疫疗法的有效性。
临床研究报告称,在基线时,有反应者体内特定类型的细菌数量比无反应者更多,尤其是嗜黏蛋白阿克曼氏菌、瘤胃球菌科、粪杆菌属和毛螺菌科。食用高纤维饮食后,肠道中的细菌将膳食纤维发酵成短链脂肪酸(SCFA),如乙酸盐、丙酸盐和丁酸盐。一些短链脂肪酸滋养肠道上皮细胞,一些则进入血液。在这里,短链脂肪酸可以激活DC8 + 细胞毒性T细胞,诱导癌细胞死亡。饮食中高纤维摄入量与检查点免疫疗法期间疾病进展或死亡风险降低有关。最近的研究结果表明,以植物为基础的高纤维饮食,如地中海饮食,对肠道微生物群有积极影响,而抗生素和质子泵抑制剂会通过改变肠道微生物群对癌症免疫疗法的结果产生负面影响。这篇叙述性综述提供了细菌类型及其代谢产物与对检查点免疫疗法的良好反应之间存在关联的证据。需要进行前瞻性临床试验来确定饮食干预是否可以改善治疗结果。