MYC-PDL1 axis reduces sensitivity to nivolumab in recurrent head and neck squamous cell carcinoma
MYC-PDL1 axis reduces sensitivity to nivolumab in recurrent head and neck squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2021.105666
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发表时间：
2021-12-09
期刊：
影响因子：
4.8
通讯作者：
Harada, Hiroyuki
中科院分区：
文献类型：
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作者：
Noji, Rika;Kano, Yoshihito;Harada, Hiroyuki
复发性或转移性头颈部鳞状细胞癌（R/M HNSCC）患者预后较差。最近，免疫检查点抑制剂（ICIs）在药物治疗中的应用一直在扩大。然而，免疫治疗的应答率很低。因此，需要对各种类型的恶性肿瘤进行ICIs反应和耐药的预测性生物标志物的鉴定。我们报告了一例复发性和转移性HNSCC患者，他们在转移性病变中同时对纳武单抗表现出不同的反应。在给予纳武单抗后，转移到多个颈部淋巴结的转移率显著降低，而新的转移到右侧腋窝淋巴结发生了。每个手术标本都使用癌症基因面板测试（FoundationOne CDx）进行分析，以阐明为什么同一患者的治疗反应不同。下一代测序显示MYC扩增和右侧腋窝淋巴结的程序性细胞死亡-1缺失，但颈部淋巴结没有。此外，组织病理学结果表明，MYC扩增调节程序性死亡配体1的表达，并参与了对ICIs反应的降低。这一结果有望帮助预测ICI治疗的疗效和选择治疗药物。
Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) have a poor prognosis. Recently, the use of immune checkpoint inhibitors (ICIs) for drug treatment has been expanding . However, the response rate to immunotherapy is low. Therefore, the identification of predictive biomarkers of response and resistance to ICIs is required for various types of malignant tumors. We report the case of a patient with recurrent and metastatic HNSCC who simultaneously showed different responses to nivolumab in metastatic lesions. After administering nivolumab, metastasis to the multiple cervical lymph node metastases showed a significant reduction, whereas a new metastasis to the right axillary lymph node occurred . Each surgical specimen was analyzed using the cancer gene panel test (FoundationOne CDx) to elucidate why treatment response is distinct among the same patient. Next-generation sequencing revealed MYC amplification and programmed cell death-1 loss in the right axillary lymph nodes but not cervical lymph nodes. Furthermore, t he histopathological findings suggested that MYC amplification regulated programmed death-ligand 1 expression and was involved in a decreased response to ICIs. This result is expected to help predict the efficacy of ICI treatment and select therapeutic agents.