Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies)
Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies)
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DOI：
10.3390/ijms20153744
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Kyo, Satoru
中科院分区：
文献类型：
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作者：
Ono, Ruriko;Nakayama, Kentaro;Kyo, Satoru
去分化子宫内膜癌（DDEC）是指未分化癌与分化的子宫内膜样癌（1级或2级）的混合。与3级子宫内膜样腺癌相比，其预后较差，并且通常与错配修复（MMR）蛋白的丢失有关，这在微卫星不稳定（MSI）型子宫内膜癌中可见。最近的研究表明，免疫检查点抑制剂治疗的有效性与MMR缺陷有关，因此，我们分析了17例DDEC病例的免疫表型（MMR缺陷和PD-L1表达）。在未分化成分中，9例（53%）缺乏MMR蛋白，9例（53%）表达PD-L1。PD-L1表达与MMR缺陷显著相关（p = 0.026）。此外，肿瘤浸润淋巴细胞（CD 8+）的存在与MMR缺陷显著相关（p = 0.026）。相比之下，没有一个病例在分化良好的成分中显示PD-L1表达。我们的研究结果表明，DDEC可能是免疫检查点抑制剂（抗PD-L1/PD-1抗体）的靶点，特别是在未分化成分中。作为DDEC的治疗策略，传统的紫杉醇加卡铂和顺铂加多柔比星治疗对分化良好的患者有效。然而，通过使用免疫检查点抑制剂与其他常规治疗相结合，有可能控制未分化成分并改善预后。
Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (p = 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (p = 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.