CMTM6 expression in M2 macrophages is a potential predictor of PD-1/PD-L1 inhibitor response in colorectal cancer.
CMTM6 expression in M2 macrophages is a potential predictor of PD-1/PD-L1 inhibitor response in colorectal cancer.
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M2 巨噬细胞中的 CMTM6 表达是结直肠癌中 PD-1/PD-L1 抑制剂反应的潜在预测因子
DOI：
10.1007/s00262-021-02931-6
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Liang L
中科院分区：
文献类型：
--
作者：
Wu X;Lan X;Hu W;Zhang W;Lai X;Xu S;Li J;Qiu W;Wang W;Xiao J;Wang F;Ding Y;Liang L
背景CMTM6是PD-L1的一个新的关键调节因子。CMTM6和PD-L1的高表达可能预示着PD-1轴阻断对肺癌的益处。本研究旨在研究错配修复缺陷(DMMR)和错配修复熟练(PMMR)结直肠癌组织中CMTM6的表达模式及其与PD-1/PD-L1通路阻断反应的相关性。方法采用免疫组织化学方法检测错配修复缺陷(DMMR)和错配修复熟练(PMMR)结直肠癌组织中CMTM6和PD-L1的表达及免疫细胞密度。采用免疫荧光技术检测经PD-1/PD-L1抑制剂治疗的结直肠癌患者外周血中CMTM6、PD-L1、CD4、CD8、CD68和CD163的表达。DMMR结直肠癌患者CMTM6、PD-L1表达及CD4+、CD8+、CD68+或CD163+细胞密度显著高于pMMR结直肠癌患者。DMMR结直肠癌中CMTM6表达与PD-L1表达及CD163+M2巨噬细胞密度呈正相关。IF分析显示，CMTM6/PD-L1共表达率及CMTM6在CD8+T细胞和CD163+M2巨噬细胞中的表达率在临床受益组显著增加。M2巨噬细胞中CMTM6的表达是预测PD-1/PD-L1抑制剂疗效的最佳生物标志物。结论M2巨噬细胞中CMTM6的表达可以比dMMR/微卫星不稳定高状态(MSI-H)更准确地预测结直肠癌患者PD-1/PD-L1抑制剂的应答率。它还可以确定哪些pMMR结直肠癌患者可以受益于PD-1/PD-L1抑制剂。
BackgroundCMTM6 is a novel key regulator of PD-L1. High expression of both CMTM6 and PD-L1 may predict the benefit of PD-1 axis blockade in lung cancer. We aimed to investigate the expression pattern of CMTM6 between mismatch repair-defective (dMMR) and mismatch repair-proficient (pMMR) colorectal cancer (CRC) tissues and assess its correlation with the response to PD-1/PD-L1 pathway blockade.MethodsImmunohistochemistry (IHC) was used to analyze CMTM6 and PD-L1 expression and immune cell density in dMMR/pMMR CRC. Quantitative multiplex immunofluorescence (IF) was performed to detect CMTM6, PD-L1, CD4, CD8, CD68 and CD163 expression in CRC patients treated with PD-1/PD-L1 inhibitors.ResultIHC analysis showed that CMTM6 and PD-L1 were both expressed in tumor cells (TCs) and invasion front immune cells (ICs). CMTM6 and PD-L1 expression and CD4+, CD8+, CD68+or CD163+cell density were significantly higher in dMMR CRC patients than in pMMR CRC patients. CMTM6 expression was positively correlated with PD-L1 expression and CD163+M2 macrophage density in dMMR CRC. IF analysis showed that the coexpression rate of CMTM6/PD-L1 and the expression rate of CMTM6 in CD8+T cells and CD163+M2 macrophages were significantly increased in the group that exhibited clinical benefit. CMTM6 expression in M2 macrophages was identified as the best biomarker for predicting the responsiveness to PD-1/PD-L1 inhibitors.ConclusionsCMTM6 expression in M2 macrophages may predict the PD-1/PD-L1 inhibitor response rate in CRC patients more accurately than dMMR/microsatellite instability-high (MSI-H) status. It can also identify pMMR CRC patients who could benefit from PD-1/PD-L1 inhibitors.
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结直肠癌癌细胞和肿瘤浸润淋巴细胞中程序性细胞死亡 1 (PD-1) 和 PD-配体 1 (PD-L1) 表达的预后影响
影响因子：
37.3
作者：
Li Y;Liang L;Dai W;Cai G;Xu Y;Li X;Li Q;Cai S
通讯作者：
Cai S
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
64.8
作者：
Burr ML;Sparbier CE;Chan YC;Williamson JC;Woods K;Beavis PA;Lam EYN;Henderson MA;Bell CC;Stolzenburg S;Gilan O;Bloor S;Noori T;Morgens DW;Bassik MC;Neeson PJ;Behren A;Darcy PK;Dawson SJ;Voskoboinik I;Trapani JA;Cebon J;Lehner PJ;Dawson MA
通讯作者：
Dawson MA
DOI：
10.1016/s0140-6736(16)00561-4
发表时间：
2016-05-07
期刊：
Lancet (London, England)
影响因子：
--
作者：
Rosenberg JE;Hoffman-Censits J;Powles T;van der Heijden MS;Balar AV;Necchi A;Dawson N;O'Donnell PH;Balmanoukian A;Loriot Y;Srinivas S;Retz MM;Grivas P;Joseph RW;Galsky MD;Fleming MT;Petrylak DP;Perez-Gracia JL;Burris HA;Castellano D;Canil C;Bellmunt J;Bajorin D;Nickles D;Bourgon R;Frampton GM;Cui N;Mariathasan S;Abidoye O;Fine GD;Dreicer R
通讯作者：
Dreicer R
影响因子：
2.7
作者：
Gao, Feng;Chen, Jing;Ji, Yong
通讯作者：
Ji, Yong