Department of Medical Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) and Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Hangzhou YITU Healthcare Technology Co., Ltd., Hangzhou, China.
Thorac Cancer. 2021 Aug;12(15):2170-2181. doi: 10.1111/1759-7714.14046. Epub 2021 Jun 15.
The prognosis for patients with stage II/III non-small cell lung cancer (NSCLC) is unsatisfactory, even after complete tumor resection and adjuvant chemotherapy. Here, we assessed the prognostic and predictive value of immunogenomic signatures for stage II/III NSCLC in Chinese patients.
A total of 91 paired resected stage II/III NSCLC and normal tissues, including 47 squamous cell lung carcinomas (SCC) and 44 lung adenocarcinomas (ADC), were collected and analyzed using whole exome sequencing (WES) to identify immunogenomic signatures for association with clinicopathological variables and disease-free survival (DFS).
Higher neoantigen load (NAL, >2 neoantigens/Mb) exhibited better DFS for SCC patients (p = 0.021) but not ADC patients. A benefit from adjuvant chemotherapy was correlated with lower NAL (≤2 neoantigens/Mb) (p = 0.009). However, tumor mutation burden (TMB), mutations of individual gene, oncogene pathways, and antigen presentation machinery genes, and human leukocyte antigen (HLA)-I number and HLA-I loss of heterozygosity (LOH) had no prognostic or predictive value for DFS of SCC or ADC patients.
NAL is a useful biomarker for lung SCC prognosis and prediction of chemotherapy responses in Chinese patients. The predictive value of NAL for adjuvant immunotherapy should be further explored in patients with resected NSCLC.
即使在完全肿瘤切除和辅助化疗后，II/III 期非小细胞肺癌（NSCLC）患者的预后仍不理想。在此，我们评估了免疫基因组特征对中国 II/III 期 NSCLC 患者的预后和预测价值。
共收集了 91 对 II/III 期 NSCLC 及正常组织，包括 47 例鳞癌（SCC）和 44 例肺腺癌（ADC），进行全外显子测序（WES）以识别与临床病理变量和无病生存（DFS）相关的免疫基因组特征。
高新生抗原负荷（NAL，>2 个新生抗原/Mb）与 SCC 患者的 DFS 更好相关（p=0.021），但与 ADC 患者无关。辅助化疗的获益与较低的 NAL（≤2 个新生抗原/Mb）相关（p=0.009）。然而，肿瘤突变负荷（TMB）、个别基因的突变、致癌基因途径和抗原呈递机制基因，以及人类白细胞抗原（HLA）-I 数量和 HLA-I 杂合性丢失（LOH）对 SCC 或 ADC 患者的 DFS 均无预后或预测价值。
NAL 是中国 SCC 患者预后和化疗反应预测的有用生物标志物。NAL 对辅助免疫治疗的预测价值应在接受 NSCLC 切除治疗的患者中进一步探讨。
