粟粒型肺癌的肿瘤微环境及其与EGFR⁃TKI疗效的关系

Tumor microenvironment of miliary lung cancer and its relationship with efficacy of EGFR⁃TKI

目的探讨肿瘤免疫微环境对粟粒型肺癌患者接受靶向治疗疗效的影响。方法回顾性分析2017年3月至2019年3月广州市胸科医院诊治的147例表皮生长因子受体(EGFR)突变阳性晚期非小细胞肺癌(NSCLC)患者。根据影像学特征将患者分为粟粒型肺癌组(A组,49例)和非粟粒型肺癌组(B组,98例)。比较两组患者肿瘤微环境的差异,并分析肿瘤微环境的免疫特征及其与EGFR⁃TKI疗效的关系。结果A组PD⁃L1和CD8的阳性率分别为40.82%、53.06%,与B组(24.49%和29.59%)比较差异均有统计学意义(P<0.05)。A组I型免疫表型的比例明显高于B组(24.49%vs.10.20%,P=0.022)。A组I型与Ⅱ/Ⅲ/Ⅳ型免疫表型患者的中位PFS分别为5.7个月和7.4个月,差异有统计学意义(P=0.024);B组分别为6.0和11.0个月,差异有统计学意义(P=0.027)。结论炎症型肿瘤微环境可能影响粟粒型肺癌患者接受EGFR⁃TKI治疗的疗效。

Objective To evaluate the efficacy of epidermal growth factor receptor tyrosine kinase inhibi⁃tor(EGFR⁃TKI)on miliary lung cancer,and to explore the immunophenotyping of tumor microenvironment(TME)and its correlation with the effect of EGFR⁃TKI.Methods We retrospectively analyzed 147 patients with stage IV non⁃small cell lung cancer(NSCLC)who had EGFR mutation and received EGFR⁃TKI treatment in Guangzhou Chest Hospital from March 2017 to March 2019.According to imaging diagnosis,the patients were divided into miliary lung cancer group(group A,n=49)and non⁃miliary lung cancer group(group B,n=98).The efficacy of targeted therapy was compared between the two groups,and the immunophenotyping of TME and its relationship with the efficacy of EGFR⁃TKI were analyzed.Results The positive rates of PD⁃L1 and CD8 in group A were 40.82%and 53.06%,respectively,which were significantly higher than those in group B(24.49%and 29.59%).In group A,the median progression⁃free survival time(PFS)of patients with type I TME was significantly worse than that of typeⅡ/Ⅲ/Ⅳ(5.7 months vs.7.4 months,P=0.024);the same was true in group B(6.0 months and 11.0 months,P=0.027).Conclusion Patients with miliary lung cancer benefit poorly from EGFR⁃TKI.The inflammatory immune microenvironment may contribute to the poor efficacy of EGFR⁃TKI in these patients.