SLAMF8 expression predicts the efficacy of anti-PD1 immunotherapy in gastrointestinal cancers.
SLAMF8 expression predicts the efficacy of anti-PD1 immunotherapy in gastrointestinal cancers.
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SLAMF8表达预测抗PD1免疫疗法在胃肠道癌症中的疗效
DOI：
10.1002/cti2.1347
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发表时间：
2021
影响因子：
5.8
通讯作者：
Qian X
中科院分区：
文献类型：
--
作者：
Zhang Q;Cheng L;Qin Y;Kong L;Shi X;Hu J;Li L;Ding Z;Wang T;Shen J;Yang Y;Yu L;Liu B;Liu C;Qian X
Epstein-Barr 病毒 (EBV) 感染与抗 PD1 免疫疗法的更好反应相关。我们假设 EBV 感染引起的基因改变是关键免疫反应激活的原因，因此可以预测抗 PD1 疗效。利用胃癌（GC）的转录组数据，我们探索了 EBV 感染特异性的差异表达基因（DEG），并使用 DEG 进行共表达网络分析，以确定 EBV 阳性和 EBV 阴性 GC 组织之间一致的共表达基因（CCG）。我们选择了 CCG 的标签基因，并使用 RNA 测序和免疫组织化学对其进行了验证。我们建立了小鼠模型并收集了临床患者的组织来测试 SLAMF8 在预测抗 PD1 治疗中的价值。通过多重免疫荧光和定量 PCR 来表征 SLAMF8 的定位和表达。此外，外源过表达和RNA测序分析被用来测试SLAMF8的潜在功能。我们鉴定了 290 个 CCG，并在胃肠癌 (GI) 转录组数据中验证了标签基因 SLAMF8。我们观察到 T 细胞激活途径在高表达 SLAMF8 的胃肠道癌症中显着富集。较高的 SLAMF8 表达与 CD8 表达呈正相关，并且对抗 PD1 治疗有更好的反应。我们进一步观察到在对抗 PD1 治疗相对敏感的小鼠模型中 SLAMF8 的表达动态增加。 SLAMF8主要表达于巨噬细胞表面。巨噬细胞中 SLAMF8 的外源过度表达导致多种免疫相关途径的正向调节丰富。较高的 SLAMF8 表达可能预示着胃肠道癌症中抗 PD1 免疫疗法的疗效会更好。在这项研究中，我们发现 SLAMF8 参与激活胃肠道 (GI) 癌症的抗肿瘤免疫反应。因此，较高的 SLAMF8 表达可能预示着胃肠道癌症中抗 PD1 免疫治疗效果更好。
Epstein–Barr virus (EBV) infection is associated with a better response to anti‐PD1 immunotherapy. We hypothesised that genetic alterations induced by EBV infection are responsible for the activation of key immune responses and hence are predictive of anti‐PD1 efficacy. With transcriptome data of gastric cancer (GC), we explored differentially expressed genes (DEGs) specific for EBV infection and performed coexpression network analysis using the DEGs to identify the consistent coexpression genes (CCGs) between EBV‐positive and EBV‐negative GC tissues. We selected the tag genes of the CCGs and validated them using RNA sequencing and immunohistochemistry. We established murine models and collected tissues from clinical patients to test the value of SLAMF8 in predicting anti‐PD1 treatment. The location and expression of SLAMF8 were characterised by multiplex immunofluorescence and quantitative PCR. Moreover, exogenous overexpression and RNA‐sequencing analysis were used to test the potential function of SLAMF8. We identified 290 CCGs and validated the tag gene SLAMF8 in transcriptome data of gastrointestinal cancer (GI). We observed that the T‐cell activation pathway was significantly enriched in high‐expression SLAMF8 GI cancers. Higher SLAMF8 expression was positively associated with CD8 expression and a better response to anti‐PD1 treatment. We further observed dynamically increased expression of SLAMF8 in murine models relatively sensitive to anti‐PD1 treatment. SLAMF8 was mainly expressed on the surface of macrophages. Exogenous overexpression of SLAMF8 in macrophages resulted in enrichment of positive regulation of multiple immune‐related pathways. Higher SLAMF8 expression may predict better anti‐PD1 immunotherapy efficacy in GI cancer. In this study, we found that SLAMF8 was involved in activating the antitumour immune response in gastrointestinal (GI) cancer. Thus, higher SLAMF8 expression may predict better anti‐PD1 immunotherapy efficacy in GI cancer.
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影响因子：
4.3
作者：
Liu, Bing-Ya;Chen, Xue-Hua;Lin, Yan-Zhen
通讯作者：
Lin, Yan-Zhen
影响因子：
24.1
作者：
Li, Qiaoxia;Ai, Jun;Shan, Baoen
通讯作者：
Shan, Baoen
影响因子：
28.5
作者：
Long J;Lin J;Wang A;Wu L;Zheng Y;Yang X;Wan X;Xu H;Chen S;Zhao H
通讯作者：
Zhao H
影响因子：
11.8
作者：
Naseem M;Barzi A;Brezden-Masley C;Puccini A;Berger MD;Tokunaga R;Battaglin F;Soni S;McSkane M;Zhang W;Lenz HJ
通讯作者：
Lenz HJ
影响因子：
12.3
作者：
Li B;Severson E;Pignon JC;Zhao H;Li T;Novak J;Jiang P;Shen H;Aster JC;Rodig S;Signoretti S;Liu JS;Liu XS
通讯作者：
Liu XS