靶向谷氨酰胺代谢增强抗肿瘤免疫和免疫治疗的研究进展

Targeting glutamine metabolism to enhance anti-tumor immunity and immunotherapy

代谢重编程和免疫逃逸被认为是肿瘤的两大特征,在肿瘤的发生发展过程中起着重要作用。免疫检查点抑制剂的成功,开启了免疫疗法治疗肿瘤的新纪元。越来越多的证据表明,肿瘤细胞的代谢重编程有助于肿瘤免疫逃逸。肿瘤细胞处于高代谢状态,通过改变代谢途径来满足不受控制的生长和增殖需求。对谷氨酰胺的高需求导致多种类型的肿瘤对谷氨酰胺的依赖性。谷氨酰胺的代谢变化对肿瘤侵袭性和肿瘤微环境的重塑有显著影响。谷氨酰胺对免疫细胞的增殖和激活也至关重要。肿瘤细胞对谷氨酰胺的大量消耗会导致免疫抑制性肿瘤微环境,以及对免疫检查点抑制剂的耐药性。本综述总结了肿瘤细胞的谷氨酰胺代谢特征及促进肿瘤免疫逃逸的研究进展,并探讨了靶向谷氨酰胺代谢增强抗肿瘤免疫和免疫治疗的最新策略。

Metabolic reprogramming and immune escape play important roles in tumor development,recognized as two hallmarks of cancer.The success of immune checkpoint inhibitors has opened a new era of immunotherapy for cancer treatments.Accumulating evidence suggests that metabolic adaptation of cancer cells contributes to tumor immune evasion.With high levels of metabolic activity,cancer cells change metabolic pathways to meet the needs for uncontrolled growth and proliferation.The high demand for glutamine leads to many types of cancer addicted to glutamine.Altered glutamine metabolism has a significant impact on tumor invasiveness and remodeling of the tumor microenvironment.Glutamine is also a vital nutrient for the proliferation and activation of immune cells.The abundant consumption of glutamine by cancer cells can lead to immunosuppressive tumor microenvironment and resistance to immune checkpoint inhibitor therapy.In this review,we provide an updated overview of glutamine metabolism of tumor cells and its involvement in tumor immune evasion,and explore the potential applications of targeting glutamine metabolism to enhance anti-tumor immunity and immunotherapy.