Department of Biotechnology and Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid, 22110, Jordan.
Cancer Immunol Immunother. 2022 Oct;71(10):2325-2340. doi: 10.1007/s00262-022-03171-y. Epub 2022 Mar 16.
Immune checkpoint proteins, such as programmed cell death receptor 1 (PD-1) and its ligand (PD-L1), play critical roles in the pathology of chronic inflammatory pathological conditions, particularly cancer. In addition, the activation of PD-1/PD-L1 pathway is involved in mediating resistance to certain anti-cancer chemo- and immuno-therapeutics. Unfortunately, targeting the PD-1/PD-L1 pathway by the available anti-PD-1/PD-L1 drugs can benefit only a small proportion of cancer patients. Thus, studying the factors that regulate the expression of these immune checkpoint proteins is of central importance in this context. Recent investigations have identified CMTM6 and, to a lesser extent, CMTM4, as master regulators of PD-L1 expression in various cancer cells. Understanding the mechanisms by which such proteins upregulate the expression of PD-L1 in tumor cells, and determining the potential regulators of CMTM6 expression in different types of cancers will accelerate the development of new therapeutic targets and/or lead to the enhancement of the currently available PD-1/PD-L1 blockade therapies.
免疫检查点蛋白，如程序性细胞死亡受体 1（PD-1）及其配体（PD-L1），在慢性炎症性疾病的病理学中起着关键作用，特别是癌症。此外，PD-1/PD-L1 通路的激活参与介导对某些抗癌化疗和免疫治疗的耐药性。不幸的是，可用的抗 PD-1/PD-L1 药物通过靶向 PD-1/PD-L1 通路只能使一小部分癌症患者受益。因此，研究调节这些免疫检查点蛋白表达的因素在这方面至关重要。最近的研究已经确定了 CMTM6，在较小程度上确定了 CMTM4，是各种癌细胞中 PD-L1 表达的主要调节因子。了解这些蛋白如何上调肿瘤细胞中 PD-L1 的表达，以及确定不同类型癌症中 CMTM6 表达的潜在调节剂，将加速新治疗靶点的开发，并/或导致增强目前可用的 PD-1/PD-L1 阻断疗法。
