驱动基因阳性肺鳞癌的疗效及肿瘤免疫微环境探索分析

Explore and Analyze the Therapeutic Effects and Tumor Immune Microenvironment of Driver Gene⁃Positive Lung Squamous Cell Carcinoma

目的目前,关于鳞状细胞肺癌(squamous cell lung cancer,SqCLC)患者驱动基因突变的频率和最佳治疗方案存在争议。本研究的目的是分析该人群中的突变状态和不同治疗方案的疗效。方法选择2019年9月1日至2021年9月25日在广东省肺癌研究所确诊的局部晚期和晚期SqCLC患者。对所有接受基因检测的患者进行突变状态和疗效的回顾性分析。采用肿瘤患者来源的类器官(patient derived organoid,PDO)进行药敏实验,应用多重免疫组织化学(multi⁃immunohistochemistry,mIHC)初步探索肿瘤免疫微环境(tumor immune microenvironment,TIME)。结果EGFR、ALK、MET、HER2和RET的突变频率分别为7.8%、1.1%、1.2%、0.6%和0.6%。在21例驱动基因突变阳性患者中,共有14例患者接受了一线酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)治疗,客观缓解率(objective response rate,ORR)为42.9%。第三代TKI在EGFR突变患者中的ORR为80.0%。药敏试验为靶向治疗的潜在益处提供了证据。此外,mIHC结果显示驱动基因突变阳性SqCLC患者中巨噬细胞和NK细胞的不同浸润特征。结论靶向治疗对具有驱动基因突变阳性的局部晚期和晚期SqCLC患者有一定的疗效。同时,TIME与该人群靶向治疗和免疫治疗疗效之间的相关性值得探讨。

Objective At present,there are controversies regarding the frequency and optimum treatment regimen of oncogenic driver mutations in squamous cell lung carcinoma(SqCLC)patients.This study aimed to analyze the mutation status and the efficacy of different treatment regimens in this population.Methods Patients with locally advanced and advanced SqCLC diagnosed at the Guangdong Lung Cancer Institute from September 1,2019,to September 25,2021,were selected.A retrospective analysis of mutation status and efficacy was performed on all patients who underwent gene detection.To verify and explore the basis for the efficacy of different therapies,drug susceptibility tests using patient⁃derived organoids and multi⁃immunohistochemistry(mIHC)were conducted.Results The mutational frequencies of E GFR,ALK,MET,HER2 andRET were 7.8%,1.1%,1.2%,0.6%and 0.6%,respectively.Among the 21 patients with oncogenic driver mutations,a total of 14 patients received first⁃line tyrosine kinase inhibitors(TKIs),with an objective response rate(ORR)of 42.9%.The ORR of 3rd⁃generation TKIs in patients with EGFR mutations was 80.0%.Drug susceptibility tests provided evidence for the potential benefit of targeted therapy.Additionally,the mIHC results indicated the different infiltrating characteristics of macrophages and NK cells in SqCLC patients with oncogenic driver mutations.Conclusions Targeted therapy does have certain benefits in locally advanced and advanced SqCLC patients with oncogenic driver mutations.At the same time,the correlation between the tumor immune microenvironment and the efficacy of both targeted therapy and immunotherapy among this population is worth exploring.