癌症免疫治疗中代谢适应与饮食之间的相互作用
The Interplay between Metabolic Adaptations and Diet in Cancer Immunotherapy.
作者信息
Espelage Lena, Wagner Natalie, Placke Jan-Malte, Ugurel Selma, Tasdogan Alpaslan
机构信息
Department of Dermatology, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany.
出版信息
Clin Cancer Res. 2024 Aug 1;30(15):3117-3127. doi: 10.1158/1078-0432.CCR-22-3468.
Over the past decade, cancer immunotherapy has significantly advanced through the introduction of immune checkpoint inhibitors and the augmentation of adoptive cell transfer to enhance the innate cancer defense mechanisms. Despite these remarkable achievements, some cancers exhibit resistance to immunotherapy, with limited patient responsiveness and development of therapy resistance. Metabolic adaptations in both immune cells and cancer cells have emerged as central contributors to immunotherapy resistance. In the last few years, new insights emphasized the critical role of cancer and immune cell metabolism in animal models and patients. During therapy, immune cells undergo important metabolic shifts crucial for their acquired effector function against cancer cells. However, cancer cell metabolic rewiring and nutrient competition within tumor microenvironment (TME) alters many immune functions, affecting their fitness, polarization, recruitment, and survival. These interactions have initiated the development of novel therapies targeting tumor cell metabolism and favoring antitumor immunity within the TME. Furthermore, there has been increasing interest in comprehending how diet impacts the response to immunotherapy, given the demonstrated immunomodulatory and antitumor activity of various nutrients. In conclusion, recent advances in preclinical and clinical studies have highlighted the capacity of immune-based cancer therapies. Therefore, further exploration into the metabolic requirements of immune cells within the TME holds significant promise for the development of innovative therapeutic approaches that can effectively combat cancer in patients.
在过去十年中,通过引入免疫检查点抑制剂以及增强过继性细胞转移以强化先天性癌症防御机制,癌症免疫疗法取得了显著进展。尽管取得了这些非凡成就,但一些癌症对免疫疗法表现出抗性,患者反应有限且会产生治疗抗性。免疫细胞和癌细胞中的代谢适应已成为免疫疗法抗性的主要促成因素。在过去几年中,新的见解强调了癌症和免疫细胞代谢在动物模型和患者中的关键作用。在治疗期间,免疫细胞会发生重要的代谢转变,这对其获得的针对癌细胞的效应功能至关重要。然而,癌细胞的代谢重编程以及肿瘤微环境(TME)内的营养竞争会改变许多免疫功能,影响它们的适应性、极化、募集和存活。这些相互作用引发了针对肿瘤细胞代谢并有利于TME内抗肿瘤免疫的新型疗法的开发。此外,鉴于各种营养素已证明的免疫调节和抗肿瘤活性,人们对了解饮食如何影响免疫疗法反应的兴趣日益浓厚。总之,临床前和临床研究的最新进展突出了基于免疫的癌症疗法的能力。因此,进一步探索TME内免疫细胞的代谢需求对于开发能够有效对抗患者癌症的创新治疗方法具有重大前景。