Department of Oncology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 510080, Guangzhou, China.
Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China.
Thorac Cancer. 2023 May;14(14):1294-1305. doi: 10.1111/1759-7714.14873. Epub 2023 Apr 2.
The use of neoadjuvant immunotherapy plus chemotherapy has revolutionized the management of esophageal squamous cell carcinoma (ESCC) patients. Nevertheless, patients who would maximally benefit from these therapies have not been identified.
We collected postoperative specimens from 103 ESCC patients, of which 66 patients comprised a retrospective cohort and 37 comprised a prospective cohort. Patient specimens were subjected to applied multi-omics analysis to uncover the mechanistic basis for patient responsiveness to cancer immunotherapy. The tumor microenvironment characteristics of these patient specimens was explored and identified by multiplex immunofluorescence and immunohistochemistry.
Results demonstrated high COL19A1 expression to be a novel biomarker for successful immunotherapy (COL19A1 , odds ratio [95% confidence interval]: 0.31 [0.10-0.97], p = 0.044). Compared with COL19A1 patients, COL19A1 patients benefited more from neoadjuvant immunotherapy (p < 0.01), obtained better major pathological remissions (63.3%, p < 0.01), with a trend toward better recurrence-free survival (p = 0.013), and overall survival (p = 0.056). Moreover, analysis of an immune-activation subtype of patients demonstrated increased B cell infiltration to be associated with favorable patient survival and a better response to neoadjuvant immunotherapy plus chemotherapy.
The findings of this study provide insight into the optimal design of individual treatments for ESCC patients.
新辅助免疫治疗联合化疗已经彻底改变了食管鳞癌(ESCC)患者的治疗方式。然而,尚未确定哪些患者能从这些治疗中最大获益。
我们收集了 103 例 ESCC 患者的术后标本,其中 66 例为回顾性队列,37 例为前瞻性队列。通过应用多组学分析对患者标本进行检测,以揭示患者对癌症免疫治疗反应的机制基础。通过多重免疫荧光和免疫组化探索和鉴定这些患者标本的肿瘤微环境特征。
结果表明,COL19A1 高表达是免疫治疗成功的新生物标志物(COL19A1,比值比[95%置信区间]:0.31 [0.10-0.97],p=0.044)。与 COL19A1 患者相比,COL19A1 患者从新辅助免疫治疗中获益更多(p<0.01),获得更好的主要病理缓解(63.3%,p<0.01),无复发生存(p=0.013)和总生存(p=0.056)趋势更好。此外,对患者免疫激活亚型的分析表明,B 细胞浸润增加与患者生存良好和对新辅助免疫治疗联合化疗的反应良好相关。
这项研究的结果为 ESCC 患者的个体化治疗最佳设计提供了思路。