Clinical relevance of PD-L1 expression and CD8+T cells infiltration in patients with EGFR-mutated and ALK-rearranged lung cancer
Clinical relevance of PD-L1 expression and CD8+T cells infiltration in patients with EGFR-mutated and ALK-rearranged lung cancer
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DOI：
10.1016/j.lungcan.2018.09.010
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发表时间：
2018-11-01
期刊：
影响因子：
5.3
通讯作者：
Wu, Yi-Long
中科院分区：
文献类型：
--
作者：
Liu, Si-yang;Dong, Zhong-yi;Wu, Yi-Long
目的：EGFR突变或ALK重排的非小细胞肺癌（NSCLC）通常显示出对检查点抑制剂（CPI）不利的临床获益。然而，很少有综合分析的报告来解释PD-1/PD-L1抑制剂反应不良的潜在机制。我们回顾性分析了EGFR突变和ALK重排患者的肿瘤微环境（TME），以及TME亚型对总生存期（OS）的预测价值。材料和方法：收集广东省肺癌研究所715例肺癌患者的肿瘤标本。通过免疫组织化学（IHC）测定肿瘤PD-L1表达（N = 715）和CD 8 + T细胞浸润（N = 658），基于此将TME分为四种不同亚型：PD-L1 +/CD 8+、PD-L1-/CD 8+、PD-L1+/CD 8-、PD-L1-/CD 8-。结果：EGFR突变或ALK重排患者中，PD-L1 +/CD 8+肿瘤比例最低（5.0%，17/342），PD-L1-/CD 8-肿瘤比例最高（63.5%，217/342）。在具有野生型EGFR和ALK的患者中，14.2%（45/316）的肿瘤为PD-L1 +/CD 8+，50.3%（159/316）的肿瘤为PD-L1-/CD 8-（P < 0.001）。EGFR突变或ALK重排的肺癌的中位OS在PD-L1阳性组中为78.6个月，在PD-L1阴性组中为93.4个月（HR 0.47，95%CI 0.23-0.76，P = 0.005）。PD-L1+/CD 8+组的OS最短，为44.3个月，但可能对CPI有反应。结论：EGFR突变或ALK重排患者TME中PD-L1和CD 8共表达水平较低，可能是导致CPI疗效差的原因。EGFR突变或ALK重排的肺癌中的PD-L1和CD 8共表达是OS较短的不良预后的生物标志物。
Objectives: EGFR-mutated or ALK-rearranged non-small cell lung cancer (NSCLC) often showed unfavorable clinical benefit to checkpoint inhibitors (CPIs). However, few reports exist with integrated analysis, to interpret the underlying mechanism of poor response to PD-1/PD-L1 inhibitors. We have retrospectively analyzed the tumor microenvironment (TME) based on tumor PD-L1 expression and CD8 + T cells infiltration in patients with EGFR mutations and ALK rearrangements, and the prognostic value of TME subtypes on overall survival (OS).Materials and methods: Tumor samples from 715 patients with lung cancer were retrospectively collected at Guangdong Lung Cancer Institute. Tumoral PD-L1 expression (N = 715) and CD8 + T cells infiltration (N = 658) was determined by immunohistochemistry (IHC), based on which TME was categorized into four different subtypes: PD-L1 +/CD8 +, PD-L1-/CD8 +, PD-L1+/CD8-, PD-L1-/CD8-. Proportion of four TME subtypes was determined, and overall survival with PD-L1 expression and TME was analyzed.Results: In patients with EGFR mutations or ALK rearrangements, proportion of PD-L1 +/CD8 + tumors was the lowest (5.0%, 17/342), and that of PD-L1-/CD8- tumors was the highest (63.5%, 217/342). In patients with wild-type EGFR and ALK, 14.2% (45/316) tumors were PD-Ll +/CD8 + and 50.3% (159/316) tumors were PD-L1-/CD8- (P < 0.001). Median OS of EGFR-mutated or ALK-rearranged lung cancer was 78.6 months in PD-Ll positive group and 93.4 months in PD-Ll negative group (HR 0.47, 95%CI 0.23-0.76, P = 0.005). PD-L1+/ CD8 + group exhibited the shortest OS, with 44.3 months, but is likely to respond to CPIs. The PD-L1-/CD8 + group exhibited the longest OS but is unlikely to respond to CPIs.Conclusion: Patients with EGFR mutations or ALK rearrangements exhibited lower PD-Ll and CD8 co-expression level in TME, which could be responsible for poor response to CPIs. PD-Ll and CD8 co-expression in EGFR-mutated or ALK-rearranged lung cancer is a biomarker for poor prognosis with shorter OS.