Department of Internal Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China.
YuceBio Technology Co., Ltd, Shenzhen 51800, China.
Immunotherapy. 2021 Feb;13(3):195-200. doi: 10.2217/imt-2020-0173. Epub 2020 Nov 26.
Despite the significant success of immune checkpoint blockade therapy in advanced non-small-cell lung cancer compared with chemotherapy, efficacy varies greatly across patients, and acquired resistance frequently occurs. In particular, during immunotherapy, the dynamic changes in molecular events have not been characterized. The authors report a case of squamous cell lung carcinoma with renal metastasis, treated with pembrolizumab, in which the primary tumor and rare renal metastases showed different responses. Using whole-exome sequencing, the authors found loss of heterogeneity in genes in all tumors and high levels of intratumor heterogeneity in metastases. The increased levels of HLA loss led to therapy resistance during tumor evolution. In addition to tumor mutational burden and PD-L1, HLA loss of heterozygosity and intratumor heterogeneity should be taken into consideration during immunotherapy.
尽管与化疗相比，免疫检查点阻断疗法在晚期非小细胞肺癌中取得了显著成功，但疗效在患者之间差异很大，并且经常发生获得性耐药。特别是在免疫治疗期间，分子事件的动态变化尚未得到描述。作者报告了一例接受 pembrolizumab 治疗的鳞状细胞肺癌伴肾转移病例，其中原发肿瘤和罕见的肾转移显示出不同的反应。通过全外显子组测序，作者发现所有肿瘤中基因的异质性丧失和转移灶中肿瘤内异质性水平升高。HLA 杂合性丢失的增加水平导致肿瘤进化过程中的治疗耐药。除了肿瘤突变负担和 PD-L1 之外，在免疫治疗期间还应考虑 HLA 杂合性丢失和肿瘤内异质性。
