Relationship of Metabolic Alterations and PD-L1 Expression in Cisplatin Resistant Lung Cancer.
Relationship of Metabolic Alterations and PD-L1 Expression in Cisplatin Resistant Lung Cancer.
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DOI：
10.4172/2168-9296.1000183
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发表时间：
2017-06-01
期刊：
影响因子：
--
通讯作者：
Savaraj, N
中科院分区：
文献类型：
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作者：
Wangpaichitr, M;Kandemir, H;Savaraj, N
尽管有许多关于免疫检查点抑制剂治疗非小细胞肺癌（NSCLC）的报道，但缓解率仍然很低，但持久。因此，顺铂仍然在NSCLC的治疗中发挥主要作用。虽然有许多机制涉及顺铂耐药，但在几种顺铂耐药肿瘤中发现了代谢表型的改变和活性氧（ROS）水平的升高。这些耐药细胞变得更加依赖线粒体氧化代谢而不是葡萄糖。因此，高活性氧和代谢改变有助于上皮间质转化（EMT）。重要的是，最近的研究结果表明，EMT在上调癌细胞中的PD-L1表达方面具有关键作用。因此，顺铂耐药性很可能会导致PD-L1/PD-1的高表达，这使得它们对抗PD-1或抗PD-L1抗体治疗易感。了解癌细胞代谢重编程和免疫检查点之间的相互作用对于将代谢靶向治疗与免疫治疗相结合至关重要。
Despite numerous reports on immune checkpoint inhibitor for the treatment of non-small cell lung cancer (NSCLC), the response rate remains low but durable. Thus cisplatin still plays a major role in the treatment of NSCLC. While there are many mechanisms involved in cisplatin resistance, alteration in metabolic phenotypes with elevated levels of reactive oxygen species (ROS) are found in several cisplatin resistant tumors. These resistant cells become more reliant on mitochondria oxidative metabolism instead of glucose. Consequently, high ROS and metabolic alteration contributed to epithelial-mesenchymal transition (EMT). Importantly, recent findings indicated that EMT has a crucial role in upregulating PD-L1 expression in cancer cells. Thus, it is very likely that cisplatin resistance will lead to high expression of PD-L1/PD-1 which makes them vulnerable to anti PD-1 or anti PD-L1 antibody treatment. An understanding of the interactions between cancer cells metabolic reprogramming and immune checkpoints is critical for combining metabolism targeted therapies with immunotherapies.