Lim Sangbin, Phillips Joshua B, Madeira da Silva Luciana, Zhou Ming, Fodstad Oystein, Owen Laurie B, Tan Ming
Center for Cell Death and Metabolism, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama.
The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Cancer Res. 2017 Mar 15;77(6):1245-1249. doi: 10.1158/0008-5472.CAN-16-1647. Epub 2017 Feb 28.
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 antitumor 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 the treatment of malignant disease. .
随着免疫肿瘤学领域近期取得的成功，人们对免疫检查点调节剂（如B7家族蛋白）的作用重新燃起了兴趣。免疫检查点蛋白在细胞免疫调节中起着关键作用；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、肿瘤微环境和肿瘤特异性免疫反应，导致参与启动和维持这种反应的恶性细胞和免疫细胞发生代谢重编程。免疫细胞代谢影响免疫细胞的激活状态，并最终影响癌症中的免疫反应。肿瘤细胞可能会耗尽免疫细胞最佳生成、扩增和发挥功能所需的营养物质。它们还可能在微环境中产生有毒代谢产物，或诱导保守的抑制途径，损害免疫功能，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。
