Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Cells. 2022 Jan 5;11(1):179. doi: 10.3390/cells11010179.
Expression of immune checkpoint proteins restrict immunosurveillance in the tumor microenvironment; thus, FDA-approved checkpoint inhibitor drugs, specifically PD-1/PD-L1 and CTLA-4 inhibitors, promote a cytotoxic antitumor immune response. Aside from inflammatory signaling, immune checkpoint proteins invoke metabolic reprogramming that affects immune cell function, autonomous cancer cell bioenergetics, and patient response. Therefore, this review will focus on the metabolic alterations in immune and cancer cells regulated by currently approved immune checkpoint target proteins and the effect of costimulatory receptor signaling on immunometabolism. Additionally, we explore how diet and the microbiome impact immune checkpoint blockade therapy response. The metabolic reprogramming caused by targeting these proteins is essential in understanding immune-related adverse events and therapeutic resistance. This can provide valuable information for potential biomarkers or combination therapy strategies targeting metabolic pathways with immune checkpoint blockade to enhance patient response.
免疫检查点蛋白的表达限制了肿瘤微环境中的免疫监视；因此，美国食品和药物管理局 (FDA) 批准的检查点抑制剂药物，特别是 PD-1/PD-L1 和 CTLA-4 抑制剂，可促进细胞毒性抗肿瘤免疫反应。除了炎症信号外，免疫检查点蛋白还会引发代谢重编程，影响免疫细胞功能、自主癌细胞生物能量和患者反应。因此，本综述将重点关注目前批准的免疫检查点靶蛋白调节的免疫和癌细胞中的代谢改变，以及共刺激受体信号对免疫代谢的影响。此外，我们还探讨了饮食和微生物组如何影响免疫检查点阻断治疗的反应。靶向这些蛋白引起的代谢重编程对于理解免疫相关不良事件和治疗抵抗至关重要。这可为潜在的生物标志物或联合治疗策略提供有价值的信息，这些策略针对免疫检查点阻断的代谢途径，以增强患者的反应。
