PD-L1表达与CD8 + T细胞免疫反应在肝细胞癌中的关系

StephenW

J Immunother. 2017 Nov/Dec;40(9):323-333. doi: 10.1097/CJI.0000000000000187.
Relationship Between PD-L1 Expression and CD8+ T-cell Immune Responses in Hepatocellular Carcinoma.Huang CY1, Wang Y, Luo GY, Han F, Li YQ, Zhou ZG, Xu GL.
Author information
1*Department of Endoscopy †State Key Laboratory of Oncology in South China §Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center ‡Haizhu District Center for Disease Control and Prevention, Guangzhou, P.R. China.

AbstractAs PD-1/PD-L1 immune checkpoint inhibitors exhibited promising clinical outcomes in various types of solid tumors, PD-1/PD-L1 blockades have been explored for the treatment of hepatocellular carcinoma (HCC). However, the association of PD-L1 with antitumor immunoregulation is not clearly defined in HCC. Here, we evaluated the characteristics of PD-L1 expression, CD8 T-cell infiltration and their relationship in HCC. A total of 411 resected tumor specimens from HCC patients were immunostained for PD-L1 and CD8. Only 78 (19%) cases showed ≥5% membranous PD-L1 expression on tumor cells, although a significantly positive correlation was found between PD-L1 expression and CD8 T-cell densities. Moreover, patients with higher tumor PD-L1 expression also showed a higher hepatitis B virus load, which was also related to increased CD8 infiltration. Survival analysis suggested that both tumor and stroma PD-L1 status did not significantly affect overall survival or recurrence-free survival in patients. Although high CD8 T-cell density was overall associated with better overall survival and recurrence-free survival, its favorable prognostic value was eliminated by high tumor PD-L1 expression. Further flow cytometric and enzyme-linked immunosorbent assay (ELISA) results from the coculture of HCC cell lines with specific CD8 cytotoxic T lymphocytes (CTLs) demonstrated that CD8 CTLs remarkably upregulated PD-L1 expression on tumor cell lines by HLA class-I specificity, and the overexpression of tumor PD-L1 impaired interferon-γ secretion by CD8 CTLs in a negative feedback regulation mechanism. In conclusion, our findings reveal an interaction between PD-L1 expression and CD8 T-cell immunity in HCC, although PD-L1 is not a prognostic factor for the patients.


PMID:29028787DOI:10.1097/CJI.0000000000000187

StephenW

J Immunother。 2017年11月/ 12月; 40（9）：323-333。 doi：10.1097 / CJI.00000000000001818。
PD-L1表达与CD8 + T细胞免疫反应在肝细胞癌中的关系。
黄CY1，王毅，罗吉，韩孚，李Q，周泽，徐GL。
作者信息

1
    *内窥镜系†华南肿瘤国家重点实验室§中山大学肿瘤医院肝胆科肿瘤中心‡海珠区疾病预防控制中心广州市，中国。

抽象

由于PD-1 / PD-L1免疫检查点抑制剂在各种类型的实体瘤中表现出有希望的临床结果，已经探索了PD-1 / PD-L1阻断剂用于治疗肝细胞癌（HCC）。然而，PD-L1与抗肿瘤免疫调节的关联在HCC中没有明确定义。在这里，我们评估了PD-L1表达，CD8 T细胞浸润及其在HCC中的关系的特征。对于PD-L1和CD8，共有411例HCC患者切除的肿瘤标本免疫染色。尽管PD-L1表达与CD8 T细胞密度呈显着正相关，但78例（19％）病例肿瘤细胞膜质PD-L1表达≥5％。此外，具有较高肿瘤PD-L1表达的患者也显示较高的乙型肝炎病毒载量，这也与CD8浸润增加有关。生存分析表明，肿瘤和基质PD-L1状态均无显着影响患者的总生存期或无复发生存期。虽然高CD8 T细胞密度总体上与更好的总体生存和无复发生存相关，但其有利的预后价值被高肿瘤PD-L1表达消除。来自HCC细胞系与特异性CD8细胞毒性T淋巴细胞（CTL）的共培养的进一步流式细胞术和酶联免疫吸附测定（ELISA）证明CD8 CTL通过HLA I类特异性显着上调肿瘤细胞系上的PD-L1表达，并且肿瘤PD-L1的过度表达受到CD8 CTLs在负反馈调节机制中的干扰素-γ分泌的损害。总之，我们的研究结果揭示了PD-L1表达与HCC中CD8 T细胞免疫的相互作用，尽管PD-L1不是患者的预后因素。

结论：
    29028787
DOI：
    10.1097 / CJI.0000000000000187