Interplay between Immune Checkpoint Proteins and Cellular Metabolism.
Interplay between Immune Checkpoint Proteins and Cellular Metabolism.
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DOI：
10.1158/0008-5472.can-16-1647
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发表时间：
2017-03-15
期刊：
影响因子：
11.2
通讯作者：
Tan M
中科院分区：
文献类型：
--
作者：
Lim S;Phillips JB;Madeira da Silva L;Zhou M;Fodstad O;Owen LB;Tan M
随着最近在免疫肿瘤学方面的成功，对免疫检查点调节剂如B7家族蛋白的作用的新兴趣已经升级。免疫检查点蛋白在调节细胞免疫中起着至关重要的作用;然而，它们对癌症生物学其他方面的贡献仍不清楚。越来越多的证据表明，免疫检查点蛋白可以调节肿瘤的代谢能量学、肿瘤微环境和肿瘤特异性免疫应答，导致恶性细胞和参与安装和维持这种应答的免疫细胞的代谢重编程。免疫细胞代谢影响免疫细胞的活化状态，并最终影响癌症中的免疫应答。肿瘤细胞可能会耗尽免疫细胞最佳生成、扩增和功能所需的营养物质。它们还可能在微环境中产生毒性代谢物或诱导损害免疫功能的保守抑制途径，从而抑制抗肿瘤反应。在这篇综述中，我们将讨论免疫检查点蛋白表达改变的癌细胞如何通过改变细胞和微环境代谢来有效抑制免疫功能，为这些途径之间的相互作用提供新的视角，并为恶性疾病的治疗提供潜在的治疗干预策略。
With the recent successes in immuno-oncology, renewed interest in the role of immune checkpoint modulators such as the B7 family proteins has escalated. The immune checkpoint proteins play a crucial role in the regulation of cellular immunity; however, their contribution to other aspects of cancer biology remains unclear. Accumulating evidence indicate that immune checkpoint proteins can regulate metabolic energetics of the tumor, the tumor microenvironment, and the tumor-specific immune response, leading to metabolic reprogramming of both malignant cells and immune cells involved in mounting and sustaining this response. Immune cell metabolism impacts the activation status of immune cells and ultimately the immune response in cancer. Tumor cells may deplete nutrients that immune cells require for optimal generation, expansion, and function. They may also generate toxic metabolites in the microenvironment or induce conserved inhibitory pathways that impair immune function and thus inhibit anti-tumor responses. In this review, we will discuss how cancer cells with altered expression of immune checkpoint proteins can potently inhibit immune function through the alteration of cellular and microenvironmental metabolism, providing a new perspective on the interplay between these pathways and offering a potential therapeutic intervention strategy in treatment of malignant disease.