PD-L1 and Tumor Infiltrating Lymphocytes as Prognostic Markers in Resected NSCLC.
PD-L1 and Tumor Infiltrating Lymphocytes as Prognostic Markers in Resected NSCLC.
复制标题
DOI：
10.1371/journal.pone.0153954
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
John T
中科院分区：
文献类型：
--
作者：
Ameratunga M;Asadi K;Lin X;Walkiewicz M;Murone C;Knight S;Mitchell P;Boutros P;John T
免疫检查点抑制改变了非小细胞肺癌 (NSCLC) 的治疗模式。关于免疫浸润和程序性死亡配体 1 (PD-L1) 作为预后标志物的结果相互矛盾。我们将一组切除的 NSCLC 中的免疫浸润和 PD-L1 表达与临床病理特征相关联。使用来自连续切除的 NSCLC 的一式三份核心构建组织微阵列。对 CD8、FOXP3 和 PD-L1 进行免疫组织化学分析。 PD-L1 强表达被预先定义为肿瘤细胞阳性率大于 50%。评估匹配的淋巴结样本的 PD-L1 表达的一致性。 522 名患者中，346 名淋巴结阴性 (N0)、72 名 N1 和 109 名 N2； 265 例为腺癌 (AC)，182 例为鳞状细胞癌 (SCC)，75 例为其他癌。 24% 的病例中发现强 PD-L1 表达。在整个队列中，PD-L1 表达与生存无关。在 N2 疾病患者中，多变量分析显示，PD-L1 强表达与无病生存 (DFS) 和总生存 (OS) 显着改善相关（HR 0.49，95%CI 0.36–0.94，p = 0.031；HR 0.46，95%CI 0.26–0.80，p = 0.006）。在这个切除的队列中，只有 5% 携带 EGFR 突变，而 19% 携带 KRAS 和 23% 携带其他突变。与 EGFR 相比，KRAS 突变肿瘤更有可能高表达 PD-L1（22% vs 3%）。间质 CD8 浸润与 SCC 的 DFS 显着改善相关（HR 0.70，95%CI 0.50-0.97，p = 0.034），但与 AC 无关，而 FOXP3 不具有预后意义。匹配的淋巴结标本 (N = 53) 的 PD-L1 表达高度一致 (89%)。 PD-L1 表达在整个队列中不具有预后意义。原发肿瘤和匹配淋巴结标本中的 PD-L1 表达高度一致。 N2 疾病中观察到的生存获益需要证实。
Immune checkpoint inhibition has shifted treatment paradigms in non-small cell lung cancer (NSCLC). Conflicting results have been reported regarding the immune infiltrate and programmed death-ligand 1 (PD-L1) as a prognostic marker. We correlated the immune infiltrate and PD-L1 expression with clinicopathologic characteristics in a cohort of resected NSCLC. A tissue microarray was constructed using triplicate cores from consecutive resected NSCLC. Immunohistochemistry was performed for CD8, FOXP3 and PD-L1. Strong PD-L1 expression was predefined as greater than 50% tumor cell positivity. Matched nodal samples were assessed for concordance of PD-L1 expression. Of 522 patients, 346 were node-negative (N0), 72 N1 and 109 N2; 265 were adenocarcinomas (AC), 182 squamous cell cancers (SCC) and 75 other. Strong PD-L1 expression was found in 24% cases. In the overall cohort, PD-L1 expression was not associated with survival. In patients with N2 disease, strong PD-L1 expression was associated with significantly improved disease-free (DFS) and overall survival (OS) in multivariate analysis (HR 0.49, 95%CI 0.36–0.94, p = 0.031; HR 0.46, 95%CI 0.26–0.80, p = 0.006). In this resected cohort only 5% harboured EGFR mutations, whereas 19% harboured KRAS and 23% other. KRAS mutated tumors were more likely to highly express PD-L1 compared to EGFR (22% vs 3%). A stromal CD8 infiltrate was associated with significantly improved DFS in SCC (HR 0.70, 95%CI 0.50–0.97, p = 0.034), but not AC, whereas FOXP3 was not prognostic. Matched nodal specimens (N = 53) were highly concordant for PD-L1 expression (89%). PD-L1 expression was not prognostic in the overall cohort. PD-L1 expression in primary tumor and matched nodal specimens were highly concordant. The observed survival benefit in N2 disease requires confirmation.