The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.
The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.
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PD-1、PD-L1 表达和 CD3 T 细胞浸润与晚期胃印戒细胞癌的预后相关，是免疫治疗的潜在生物标志物
DOI：
10.18632/oncotarget.16407
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发表时间：
2017-06-13
期刊：
影响因子：
--
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Jin S;Xu B;Yu L;Fu Y;Wu H;Fan X;Wei J;Liu B
最近的数据支持免疫检查点抑制剂在胃癌治疗中的潜在重要作用。然而，关于免疫治疗标记物在胃印戒细胞癌（SRCC）中的临床意义的数据很少。我们评估了89例晚期SRCC患者的程序性细胞死亡蛋白-1（PD-1）、程序性细胞死亡配体1（PD-L1）表达、CD 3 + T细胞浸润、微卫星不稳定性（MSI）和EB病毒（EBV），以及各因素与生存的关系。所有患者均接受以5-FU为基础的一线化疗。PD-L1和PD-1分别在40.4%和18.0%的患者中表达。PD-L1和PD-1表达之间存在显著相关性（r=0.363，p<0.001）。在32.6%的样本中，4种DNA错配修复（DNA-MMR）基因蛋白中至少有1种缺失。89例中仅有1例EBV阳性，同时伴有PD-L1阳性、CD 3 + T细胞高度浸润和MSI。增加的CD 3 + T细胞数量与增加的PD-1表达（r=0.256，p=0.012）和MSI状态（r=0.208，p=0.049）相关。高CD 3 + T细胞浸润与较好的OS相关（23.7个月，95% CI：19.0-38.0 vs 15.8个月，95% CI：13.0-22.0，p=0.033），但在多变量分析后不是生存的独立预后因素（HR=0.68，95% CI：0.42-1.10，p=0.116）。CD 3 + T细胞在PD-1阳性、MSI阳性的肿瘤中浸润较多，与较好的OS相关，提示可能存在获得性免疫抵抗。对SRCC免疫微环境的癌症免疫治疗标志物的进一步研究可能会突出免疫治疗的靶点。
Recent data supports a potentially significant role for immune checkpoint inhibitors in the treatment of gastric cancer. However, there are few data on the clinical implications of immunotherapy markers in gastric signet-ring cell carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1(PD-L1), infiltration by CD3+ T cell, microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the relationship of each factor to survival in 89 advanced SRCC patients. All patients received 5-FU-based first-line chemotherapy. PD-L1 and PD-1 were expressed in 40.4% and 18.0% of the patients, respectively. There was a significant correlation between PD-L1 and PD-1 expression (r=0.363, p<0.001). There was loss of at least 1 of the 4 DNA mismatch repair (DNA-MMR) gene proteins in 32.6% of samples. Only 1 case out of 89 was EBV positive, with concurrent PD-L1 positivity, a high degree of CD3+ T cell infiltration and MSI. Increased CD3+ T cells numbers was associated with increased PD-1 expression (r=0.256, p=0.012) and MSI status (r=0.208, p=0.049). High CD3+ T cell infiltration was related to better OS (23.7 months, 95% CI: 19.0-38.0 vs 15.8 months, 95% CI: 13.0-22.0, p=0.033), but was not an independent prognostic factor for survival after multivariate analysis (HR=0.68, 95% CI: 0.42-1.10, p=0.116). CD3+ T cell was more infiltrated in PD-1 positive, tumors with MSI and were associated with better OS, indicating an adaptive immune resistance may be occurring. Further research into the cancer immunotherapy markers of SRCC immune microenvironment may highlight targets for immunotherapy.
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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：
3.3
作者：
Falchetti, Mario;Saieva, Calogero;Ottini, Laura
通讯作者：
Ottini, Laura
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
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
影响因子：
168.9
作者：
Fuchs, Charles S.;Tomasek, Jiri;Tabernero, Josep
通讯作者：
Tabernero, Josep