Association Between Intra-Tumoral Immune Response and Programmed Death Ligand 1 (PD-L1) in Gastric Cancer
Association Between Intra-Tumoral Immune Response and Programmed Death Ligand 1 (PD-L1) in Gastric Cancer
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胃癌瘤内免疫反应与程序性死亡配体 1 (PD-L1) 之间的关联
DOI：
10.12659/msm.916432
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发表时间：
2019-09
影响因子：
3.1
通讯作者：
Jia Lizhou
中科院分区：
文献类型：
--
作者：
Yan Rong;Yang Xiaobing;Wang Xiaolei;Wang Bin;Zhao Youcai;Huang Wenbin;Zhao Wei;Jia Lizhou
PD-1/PD-L1免疫检查点靶向治疗在包括胃癌在内的多种实体瘤中表现出优异的临床结局。然而，胃癌的肿瘤微环境非常复杂，PD-L1与胃癌肿瘤微环境的关系尚不清楚。材料/方法分析478例胃癌组织中PD-L1的表达特点，采用免疫组化方法检测CD 8、CD 4肿瘤浸润白细胞（TILs）的表达，并与70例癌旁组织、32例胃良性病变组织进行比较。采用标准化方法评估胃癌中的TIL。结果PD-L1在胃癌组织中的阳性表达率为40.37%（193/478），癌旁组织中阳性表达率为20.00%（14/70），良性胃组织中阳性表达率为31.25%（10/32）。胃癌患者肿瘤细胞中PD-L1阳性状态（tPD-L1）与远处转移有关（χ2=3.344，P=0.044）。tPD-L1的阳性表达模式与TIL的高密度相关，并且与转移组相比，这种模式在无转移组中最为显著。我们还发现，tPD-L1对胃癌患者的总生存期没有预测作用，但在单变量分析中，胃癌患者中tPD-L1和tCD 8联合阳性状态与更好的总生存率密切相关[风险比（HR）=2.341，95%置信区间（CI）=1.147-3.556，P<0.001，多因素分析HR=1.844，95% CI=1.136-2.592，P=0.031。结论胃癌组织中tPD-L1的表达与肿瘤浸润淋巴细胞之间存在交互作用，且tPD-L1的表达与tCD 8的高表达呈正相关，提示胃癌患者的生存率和转移率较低。
Background Targeting of PD-1/PD-L1 immune checkpoints exhibits excellent clinical outcomes in numerous types of solid tumors, including gastric cancer. However, the tumor microenvironment of gastric cancer is very complex and the association of PD-L1 with the tumor microenvironment in gastric cancer is still not clear. Material/Methods This study analyzed the characteristics of PD-L1 expression and used immunohistochemistry to assess CD8 and CD4 tumor-infiltrating leucocytes (TILs) in 478 cases of gastric cancer compared with the expression patterns in 70 matched adjacent tissues, and 32 cases of benign gastric tissues. Standardized methods for TILs assessment in gastric cancer were used. Results The results indicated that PD-L1 expression was increased in gastric cancer tissues (193 out of 478, 40.37%) compared with matched adjacent tissues (14 out of 70, 20.00%) and benign gastric tissues (10 out of 32, 31.25%). It was observed that in gastric cancer patients, positive PD-L1 status in tumor cells (tPD-L1) was associated with distant metastasis (χ2=3.344, P=0.044). The positive expression pattern of tPD-L1 was associated with higher density of TILs, and this pattern was most significant in the non-metastasis group, compared to the metastasis group. We also found that tPD-L1 was not prognostic for overall survival in gastric cancer patients, but tPD-L1 and tCD8 combined positive status in gastric cancer patients was strongly associated with better overall survival rates both in the univariate analysis [hazard ratio (HR)=2.341, 95% confidence interval (CI)=1.147–3.556, P<0.001 and in the multivariate analysis (HR=1.844, 95% CI=1.136–2.592, P=0.031). Conclusions These data suggested an interaction between tPD-L1 expression and TILs in gastric cancer, and tPD-L1 expression positively correlated with high densities of tCD8 and indicated a better overall survival and decreased metastasis in gastric cancer patients.
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DOI：
10.1084/jem.20161594
发表时间：
2018-02-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Tober J;Maijenburg MMW;Li Y;Gao L;Hadland BK;Gao P;Minoura K;Bernstein ID;Tan K;Speck NA
通讯作者：
Speck NA
影响因子：
24.5
作者：
Thompson ED;Zahurak M;Murphy A;Cornish T;Cuka N;Abdelfatah E;Yang S;Duncan M;Ahuja N;Taube JM;Anders RA;Kelly RJ
通讯作者：
Kelly RJ
影响因子：
--
作者：
Wang ZQ;Milne K;Derocher H;Webb JR;Nelson BH;Watson PH
通讯作者：
Watson PH
影响因子：
4
作者：
Zhao W;Ding G;Wen J;Tang Q;Yong H;Zhu H;Zhang S;Qiu Z;Feng Z;Zhu J
通讯作者：
Zhu J
影响因子：
3.3
作者：
Baptista, Mauricio Z.;Sarian, Luis Otavio;Vassal, Jose
通讯作者：
Vassal, Jose