Abstract:
Immunotherapies have revolutionized the treatment of certain cancers, but challenges remain in overcoming immunotherapy resistance. Research shows that metabolic modulation of the tumor microenvironment can enhance antitumor immunity. Here, we discuss recent preclinical and clinical evidence for the efficacy of combining metabolic modifiers with immunotherapies. While this combination holds great promise, a few key areas must be addressed, which include identifying the effects of metabolic modifiers on immune cell metabolism, the putative biomarkers of therapeutic efficacy, the efficacy of modifiers on tumors harboring metabolic heterogeneity, and the potential development of resistance due to tumor reliance on alternative metabolic pathways. We propose solutions to these problems and posit that assessing these parameters is crucial for considering the potential of metabolic modifiers in sensitizing tumors to immunotherapies.
摘要:
免疫疗法彻底改变了某些癌症的治疗方法,但是在克服免疫疗法耐药性方面仍然存在挑战。研究表明,肿瘤微环境的代谢调节可以增强抗肿瘤免疫力。这里,我们讨论了代谢修饰剂与免疫疗法联合应用的近期临床前和临床证据.虽然这种组合很有希望,必须解决几个关键领域,其中包括确定代谢调节剂对免疫细胞代谢的影响,治疗功效的推定生物标志物,修饰剂对具有代谢异质性的肿瘤的功效,以及由于肿瘤对替代代谢途径的依赖而导致的耐药性的潜在发展。我们提出了这些问题的解决方案,并认为评估这些参数对于考虑代谢调节剂在使肿瘤对免疫疗法敏感方面的潜力至关重要。