Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers.
Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers.
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DOI：
10.18632/oncotarget.9076
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发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Bass AJ
中科院分区：
文献类型：
--
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
胃癌(GC)是一种致命疾病，治疗选择有限。最近对PD-1抑制的研究显示，在GC中有很好的结果，但关键问题仍然是关于哪个GC亚类的反应最好。在其他癌症中，PD-1配体PD-L1的表达已被证明可以识别对PD-1阻断有更大反应的癌症。我们在这里用免疫组织化学方法显示EB病毒(EBV)+GC(n=32)有在其他GC中未见的PD-L1表达。EBV+GC中，PD-L1在50%(16/32)的肿瘤细胞和94%(30/32)的免疫细胞中表达。在EBV阴性的GCs中，虽然35%的EBV-/MSS GCs有炎症细胞的PD-L1表达，但肿瘤细胞内PD-L1的表达仅在微卫星不稳定性(MSI)病例中可见。此外，不同类型的GC表现出不同的PD-L1+免疫细胞浸润模式。在EBV+和MSI肿瘤中，均可见PD-L1+炎性细胞浸润。相反，这些细胞仍留在EBV-/MSS GCs的肿瘤边缘。与这些发现一致的是，我们利用癌症基因组图谱研究中的GC的基因表达谱来证明，干扰素γ驱动的基因特征，另一个被建议的PD-1治疗敏感性标记，在EBV+和MSI GC中得到丰富。这些数据表明，EBV+和MSI GC患者对PD-1阻断的反应可能性更大，EBV和MSI状态应作为这些新出现的抑制剂临床试验的变量进行评估。
Gastric cancer (GC) is a deadly disease with limited treatment options. Recent studies with PD-1 inhibition have shown promising results in GC, but key questions remain regarding which GC subclass may respond best. In other cancers, expression of the PD-1 ligand PD-L1 has been shown to identify cancers with greater likelihood of response to PD-1 blockade. We here show with immunohistochemistry that Epstein-Barr Virus (EBV)+ GCs (n = 32) have robust PD-L1 expression not seen in other GCs. In EBV+ GC, we observed PD-L1 staining in tumor cells in 50% (16/32) and immune cells in 94% (30/32) of cases. Among EBV-negative GCs, PD-L1 expression within tumors cells was observed only in cases with microsatellite instability (MSI), although 35% of EBV-/MSS GCs possessed PD-L1 expression of inflammatory cells. Moreover, distinct classes of GC showed different patterns of PD-L1+ immune cell infiltrations. In both EBV+ and MSI tumors, PD-L1+ inflammatory cells were observed to infiltrate the tumor. By contrast, such cells remained at the tumor border of EBV-/MSS GCs. Consistent with these findings, we utilized gene expression profiling of GCs from The Cancer Genome Atlas study to demonstrate that an interferon-γ driven gene signature, an additional proposed marker of sensitivity to PD-1 therapy, were enriched in EBV+ and MSI GC. These data suggest that patients with EBV+ and MSI GC may have greater likelihood of response to PD-1 blockade and that EBV and MSI status should be evaluated as variables in clinical trials of these emerging inhibitors.
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影响因子：
8.8
作者：
Camargo, M. C.;Murphy, G.;Koriyama, C.;Pfeiffer, R. M.;Kim, W. H.;Herrera-Goepfert, R.;Corvalan, A. H.;Carrascal, E.;Abdirad, A.;Anwar, M.;Hao, Z.;Kattoor, J.;Yoshiwara-Wakabayashi, E.;Eizuru, Y.;Rabkin, C. S.;Akiba, S.
通讯作者：
Akiba, S.
影响因子：
11.2
作者：
Blank, C;Brown, I;Gajewski, TF
通讯作者：
Gajewski, TF
DOI：
10.1158/1078-0432.ccr-13-0855
发表时间：
2013-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chen BJ;Chapuy B;Ouyang J;Sun HH;Roemer MG;Xu ML;Yu H;Fletcher CD;Freeman GJ;Shipp MA;Rodig SJ
通讯作者：
Rodig SJ
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
破坏癌症中的 PD-1/PD-L1 免疫检查点的治疗前景：释放 CD8 T 细胞介导的抗肿瘤活性，可在各种实体瘤中产生显着的、前所未有的临床疗效。
影响因子：
10.9
作者：
Romano E;Romero P
通讯作者：
Romero P