PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma.
PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma.
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DOI：
10.1158/1078-0432.ccr-15-0715
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发表时间：
2016-01-15
期刊：
影响因子：
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通讯作者：
Ferrone CR
中科院分区：
文献类型：
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作者：
Sabbatino F;Villani V;Yearley JH;Deshpande V;Cai L;Konstantinidis IT;Moon C;Nota S;Wang Y;Al-Sukaini A;Zhu AX;Goyal L;Ting DT;Bardeesy N;Hong TS;Fernandez-del Castillo C;Tanabe KK;Lillemoe KD;Ferrone S;Ferrone CR
肝内胆管癌（ICC）需要更有效的治疗。检查点分子特异性单克隆抗体（mAb）获得的令人鼓舞的临床结果促使我们研究这种类型的免疫疗法是否适用于ICC。本研究的目的是确定(i)患者是否对其ICC产生T细胞免疫反应，（ii）检查点分子是否在T细胞和肿瘤细胞上表达，以及（iii）肿瘤细胞是否容易被同源T细胞识别。对27例ICC肿瘤分别进行T细胞和ICC细胞淋巴细胞浸润、HLA i类和HLA ii类表达、PD-1和PD-L1表达的分析。该分析结果与所调查患者的临床病理特征相关。所有肿瘤均有淋巴细胞浸润。27例肿瘤中，有8例和11例ICC细胞表达PD-L1和HLA - I类抗原。HLA I类抗原表达与CD8+ t细胞浸润相关。此外，HLA I类抗原阳性表达与PD-L1阴性/罕见表达相结合与疾病的良好临床病程相关。ICC患者可能会对自己的肿瘤产生t细胞免疫反应。ICC细胞HLA I类抗原表达缺陷与PD-L1表达结合，为其提供了免疫逃逸机制。这一机制证明了在没有HLA I类抗原表达缺陷的ICC肿瘤患者中使用检查点分子特异性单克隆抗体进行免疫治疗是合理的。
More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule-specific monoclonal antibodies (mAb) have prompted us to investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells. Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated. Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8+ T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease. ICC patients are likely to mount a T-cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression.