PD-L1 表达和 CD8+T 细胞浸润在 EGFR 突变和 ALK 重排肺癌患者中的临床意义。
Clinical relevance of PD-L1 expression and CD8+ T cells infiltration in patients with EGFR-mutated and ALK-rearranged lung cancer.
机构信息
School of Medicine, South China University of Technology, Guangzhou, 510006, China; Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
出版信息
Lung Cancer. 2018 Nov;125:86-92. doi: 10.1016/j.lungcan.2018.09.010. Epub 2018 Sep 14.
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-L1+/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-L1 positive group and 93.4 months in PD-L1 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-L1 and CD8 co-expression level in TME, which could be responsible for poor response to CPIs. PD-L1 and CD8 co-expression in EGFR-mutated or ALK-rearranged lung cancer is a biomarker for poor prognosis with shorter OS.
目的
表皮生长因子受体（EGFR）突变或间变性淋巴瘤激酶（ALK）重排的非小细胞肺癌（NSCLC）患者通常对检查点抑制剂（CPIs）的临床获益不佳。然而，目前很少有综合分析报告来解释 PD-1/PD-L1 抑制剂反应不良的潜在机制。我们回顾性分析了 715 例肺癌患者肿瘤 PD-L1 表达和 CD8+T 细胞浸润的肿瘤微环境（TME），并分析了 TME 亚型对总生存（OS）的预后价值。
材料和方法
广东肺癌研究所回顾性收集了 715 例肺癌患者的肿瘤样本。通过免疫组化（IHC）检测肿瘤 PD-L1 表达（N=715）和 CD8+T 细胞浸润（N=658），根据 TME 将其分为四种不同的亚型：PD-L1+/CD8+、PD-L1-/CD8+、PD-L1+/CD8-、PD-L1-/CD8-。确定四种 TME 亚型的比例，并分析 PD-L1 表达和 TME 的总生存情况。
结果
在 EGFR 突变或 ALK 重排的患者中，PD-L1+/CD8+肿瘤的比例最低（5.0%，17/342），PD-L1-/CD8-肿瘤的比例最高（63.5%，217/342）。在 EGFR 野生型和 ALK 重排的患者中，14.2%（45/316）的肿瘤为 PD-L1+/CD8+，50.3%（159/316）的肿瘤为 PD-L1-/CD8-（P<0.001）。PD-L1 阳性组 EGFR 突变或 ALK 重排肺癌的中位 OS 为 78.6 个月，PD-L1 阴性组为 93.4 个月（HR 0.47，95%CI 0.23-0.76，P=0.005）。PD-L1+/CD8+组的 OS 最短，为 44.3 个月，但可能对 CPIs 有反应。PD-L1-/CD8+组的 OS 最长，但可能对 CPIs 无反应。
结论
EGFR 突变或 ALK 重排的患者 TME 中 PD-L1 和 CD8 共表达水平较低，这可能是 CPIs 反应不佳的原因。EGFR 突变或 ALK 重排肺癌中 PD-L1 和 CD8 的共表达是预后不良、OS 较短的生物标志物。
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