Shimoda Yukiko, Shibaki Ryota, Yoshida Tatsuya, Murakami Shuji, Shirasawa Masayuki, Torasawa Masahiro, Matsumoto Yuji, Masuda Ken, Shinno Yuki, Okuma Yusuke, Goto Yasushi, Horinouchi Hidehito, Yamamoto Noboru, Ohe Yuichiro, Motoi Noriko
Department of Thoracic Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan; Cancer Medicine, Cooperative Graduate School, The Jikei University Graduate School of Medicine, Tokyo, Minato-ku, Tokyo, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan; Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
Clin Lung Cancer. 2022 Sep;23(6):477-486. doi: 10.1016/j.cllc.2022.04.001. Epub 2022 Apr 29.
The effectiveness of PD-1 blockade therapy in advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is limited. We investigated whether patient characteristics, PD-L1 expression, and immune cell (IC) status in the tumor microenvironment (TME) were associated with PD-1 blockade therapy outcomes.
We retrospectively reviewed patients with advanced EGFR-mutant NSCLC treated with PD-1 blockade (nivolumab or pembrolizumab) between January 2016 and March 2018. The PD-L1 expression tumor proportion score (TPS) and types and distribution of ICs (CD8, PD-1, CD204, tumoral, and stromal) in the TME were analyzed.
Among 57 EGFR-mutant NSCLC patients treated with PD-1 blockade, 39 patients had sufficient tissues for analyzing the TME. The overall response rate (ORR) of PD-1 blockade was 12.3%. Only tumoral CD8 positive (CD8) IC status was significantly associated with the response (median tumoral CD8ICs: 299/mm vs. 115/mm, P < .01). Among the 6 patients with concurrent high PD-L1 expression (TPS: ≥ 50%)/high tumoral CD8 ICs (≥ 205/mm), 5 (83.3%) showed a response and a significantly longer progression-free survival (PFS) (PFS: 9.4M vs. 1.8M, P < .01). In contrast, none of the 7 patients with high PD-L1 expression/low tumoral CD8ICs (<205/mm) showed a response.
Concurrent high PD-L1 expression and high tumoral CD8 ICs could predict the response and longer PFS of PD-1 blockade therapy in EGFR-mutant patients.
程序性死亡蛋白1（PD-1）阻断疗法在晚期表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）中的疗效有限。我们研究了患者特征、PD-L1表达以及肿瘤微环境（TME）中的免疫细胞（IC）状态是否与PD-1阻断疗法的结果相关。
我们回顾性分析了2016年1月至2018年3月期间接受PD-1阻断治疗（纳武单抗或派姆单抗）的晚期EGFR突变NSCLC患者。分析了TME中PD-L1表达的肿瘤比例评分（TPS）以及IC的类型和分布（CD8、PD-1、CD204、肿瘤和基质）。
在57例接受PD-1阻断治疗的EGFR突变NSCLC患者中，39例患者有足够的组织用于分析TME。PD-1阻断的总体缓解率（ORR）为12.3%。只有肿瘤CD8阳性（CD8）IC状态与缓解显著相关（肿瘤CD8ICs中位数：299/mm对115/mm，P < 0.01）。在6例同时具有高PD-L1表达（TPS：≥50%）/高肿瘤CD8 ICs（≥205/mm）的患者中，5例（83.3%）出现缓解，且无进展生存期（PFS）显著更长（PFS：9.4个月对1.8个月，P < 0.01）。相比之下，7例高PD-L1表达/低肿瘤CD8ICs（<205/mm）的患者均未出现缓解。
同时高PD-L1表达和高肿瘤CD8 ICs可预测EGFR突变患者对PD-1阻断疗法的反应和更长的PFS。
