Four distinct immune microenvironment subtypes in gastric adenocarcinoma with special reference to microsatellite instability.
Four distinct immune microenvironment subtypes in gastric adenocarcinoma with special reference to microsatellite instability.
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DOI：
10.1136/esmoopen-2018-000326
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发表时间：
2018
期刊：
影响因子：
7.3
通讯作者：
Kim KM
中科院分区：
文献类型：
--
作者：
Cho J;Chang YH;Heo YJ;Kim S;Kim NK;Park JO;Kang WK;Lee J;Kim KM
程序性死亡配体1(PD-L1)可在EB病毒(EBV)阳性(EBV+)或微卫星不稳定性高(MSI-H)胃癌(GC)亚型以外的肿瘤中过度表达。我们的目的是确定GC的肿瘤免疫微环境(TME)分类，以更好地了解肿瘤与免疫的相互作用，并帮助患者选择未来的免疫治疗，特别是参考MSI-H。应用免疫组织化学方法对43例EB病毒阳性、79例MSI-H和125例EB病毒−/MS患者的PD-L1和CD8+T细胞进行免疫组织化学分析。在66例MSI-H GC中，比较突变计数与PD-L1表达和患者生存期的关系。GCTME除以PD-L1IHC和肿瘤浸润性淋巴细胞(TIL)显示：(1)约40%的GC是I型(PD-L1+/TIL+)，约占MSI-H或EB病毒+GC的70%，EB病毒−/微卫星 稳定(MSS)GC患者中约15%的无病生存率(HR 2.044)和总生存率(HR 1.993)最好，这种类型对检查点阻断治疗有反应；(2)近30%的GC是II型(PD-L1−/TIL−)，生存最差；(3)约10%的GC为III型(PD-L1+/TIL−)；(4)高达20%的GC为IV型(PD-L1−/TIL+)，出乎意料的是，约25%的EBV+或MSI-H GC属于这一亚型。在MSI-H GC中，ARID1A、RNF43、NF1、MSH6、BRD3、NCOA3、BCORL1、TNKS2和NPM1发生了频繁的移码突变，且移码突变的数目与PD-L1的表达显著相关(P<；0.05)。根据PD-L1和TIL的不同，胃癌可分为四种TME类型，移码突变数目与PD-L1在MSI-H胃癌中的表达密切相关。
Programmed death-ligand 1 (PD-L1) can be overexpressed in tumours other than Epstein-Barr virus (EBV)-positive (EBV+) or microsatellite instability-high (MSI-H) gastric cancer (GC) subtypes. We aimed to determine the tumour immune microenvironment (TME) classification of GC to better understand tumour–immune interactions and help patient selection for future immunotherapy with special reference to MSI-H. Immunohistochemistry (IHC) for PD-L1 and CD8+ T cells in three distinct subtypes of GC (43 EBV+, 79 MSI-H and 125 EBV−/MSS) were performed and analysed. In 66 MSI-H GC, mutation counts were compared with PD-L1 expression and survival of the patients. GC TME divided by PD-L1 IHC and tumour-infiltrating lymphocytes (TIL) measured by intratumoural CD8 density showed: (1) about 40% of GC are type I (PD-L1+/TIL+) consisting ~70% of MSI-H or EBV+ GC, and ~15% of EBV−/microsatellite stable (MSS) GC patients show the best survival in both disease-free (HR 2.044) and overall survival (HR 1.993); this type would respond to a checkpoint blockade therapy; (2) almost 30% of GC are type II (PD-L1−/TIL−) with the worst survival; (3) approximately 10% of GC are type III (PD-L1+/TIL−); and (4) up to 20% are type IV (PD-L1−/TIL+) and, unexpectedly, ~25% of EBV+ or MSI-H GC are within this subtype. In MSI-H GC, frequent frameshift mutations were observed in ARID1A, RNF43, NF1, MSH6, BRD3, NCOA3, BCORL1, TNKS2 and NPM1 and the numbers of frameshift mutation correlated significantly with PD-L1 expression (P<0.05). GC can be classified into four TME types based on PD-L1 and TIL, and numbers of frameshift mutation correlate well with PD-L1 expression in MSI-H GC.
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影响因子：
--
作者：
Derks S;Liao X;Chiaravalli AM;Xu X;Camargo MC;Solcia E;Sessa F;Fleitas T;Freeman GJ;Rodig SJ;Rabkin CS;Bass AJ
通讯作者：
Bass AJ
影响因子：
7.4
作者：
Kawazoe, Akihito;Kuwata, Takeshi;Ochiai, Atsushi
通讯作者：
Ochiai, Atsushi
影响因子：
28.2
作者：
Llosa, Nicolas J.;Cruise, Michael;Housseau, Franck
通讯作者：
Housseau, Franck
影响因子：
--
作者：
Koh J;Ock CY;Kim JW;Nam SK;Kwak Y;Yun S;Ahn SH;Park DJ;Kim HH;Kim WH;Lee HS
通讯作者：
Lee HS
影响因子：
64.8
作者：
Herbst RS;Soria JC;Kowanetz M;Fine GD;Hamid O;Gordon MS;Sosman JA;McDermott DF;Powderly JD;Gettinger SN;Kohrt HE;Horn L;Lawrence DP;Rost S;Leabman M;Xiao Y;Mokatrin A;Koeppen H;Hegde PS;Mellman I;Chen DS;Hodi FS
通讯作者：
Hodi FS