CMTM6, the newly identified PD-L1 regulator, correlates with PD-L1 expression in lung cancers
CMTM6, the newly identified PD-L1 regulator, correlates with PD-L1 expression in lung cancers
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DOI：
10.1016/j.bbrep.2019.100690
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发表时间：
2019-12-01
影响因子：
2.7
通讯作者：
Ji, Yong
中科院分区：
文献类型：
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作者：
Gao, Feng;Chen, Jing;Ji, Yong
调节免疫检查点调节因子，尤其是PD-1/PD-L1轴，在成功治疗一小部分肺癌患者中起着关键作用，但在其余肺癌患者中并不那么有效。因此，更好地了解免疫治疗无应答或耐药患者，有助于未来开发新的治疗方法。据报道，新发现的调节因子CMTM 6（CKLF样MARVEL跨膜结构域包含6）可作为PD-L1的稳定剂，并在细胞系和动物模型中增强PD-L1对免疫系统的抑制作用，但其与PD-L1相关的临床相关性尚不清楚，目前的研究旨在解决这一问题。使用免疫组织化学的研究表明，使用我们的内部组织微阵列的19种癌症中有15种CMTM 6阳性，并且PD-L1表达总是仅在CMTM 6阳性癌症中发现。分析了81例肺癌患者样本中CMTM 6和PD-L1的表达，我们观察到CMTM 6表达与癌症组织类型相关，与癌症转移呈负相关，但与患者的年龄和性别无关。在阴性CMTM 6样本中未观察到PD-L1表达。PD-L1的高表达也与CMTM 6的高表达相关。总之，CMTM 6表达与PD-L1表达以及肺癌组织型和转移相关。因此，从临床分析的角度来看，该结果首次证实了早期关于CMTM 6/PD-L1连接的报告。
Modulation of Immune check point regulators, especially the PD-1/PD-L1 axis, plays a critical role in successful management of a small proportion of lung cancer patients, but not so effective in the rest of lung cancer patients. A better understanding of immunotherapy non-responsive or resistant patients therefore warranted for future development of novel therapeutics. The newly identified regulator CMTM6 (CKLF-like MARVEL transmembrane domain containing 6) has been reported to serves as the stabilizer of PD-L1 and enhances the inhibitory effect of PD-L1 on immune system in both cell line and animal models, but its clinical relevance associated with PD-L1 is unknown and the current study is designed to address this question. The study using immunohistochemistry demonstrated that CMTM6 positivity from 15 out of 19 types of cancers with our in-house tissue microarray, and PD-L1 expression is always found only in CMTM6 positive cancers. CMTM6 and PD-L1 expression were analyzed in 81 lung cancer patient sample, and we observed that CMTM6 expression correlated with cancer histotypes and inversely correlated with cancer metastases, but not with patients' age and gender. No PD-L1 expression was observed in negative CMTM6 samples. Higher expression PD-L1 is also associated with higher CMTM6 expression. In summary, CMTM6 expression is associated with PD-L1 expression, as well as lung cancer histotypes and metastasis. The results thus for the first time confirmed earlier reports on CMTM6/PD-L1 connection, from a clinical aspect of analysis.