Division of Oncology/Hematology, Department of Internal Medicine, Myongji Hospital, Goyang-si Gyeonggi-do, Republic of Korea.
Department of Pathology, Korea University Medical Center, Anam Hospital, Seoul, Republic of Korea.
J Thorac Oncol. 2018 May;13(5):636-648. doi: 10.1016/j.jtho.2018.01.008. Epub 2018 Jan 31.
The immune microenvironment of high-grade neuroendocrine carcinoma of the lung, including programmed death ligand 1 (PD-L1) expression, has not been well characterized.
On the basis of immunohistochemistry (IHC) results, PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) was scored as follows: TC0 and IC0 were defined as PD-L1 expression less than 1%, TC1 and IC1 as at least 1% but less than 10%, TC2 and IC2 as 10% or more but less than 50%, and TC3 and IC3 as 50% or more. Phosphatase and tensin homolog (PTEN) IHC was scored as either lost or retained expression. The Ion AmpliSeq Comprehensive Cancer Panel (ThermoFisher Scientific, Waltham, MA) was used to identify mutations in all coding exons of 409 cancer-related genes.
A total of 192 patients with large cell neuroendocrine carcinoma (LCNEC) (n = 72) and SCLC (n = 120) were studied. The prevalence of PD-L1 expression on TCs was 15.1% (29 of 192). IC infiltration and PD-L1 expression on ICs were observed in 34.4% of patients (66 of 192) and 31.3% of patients (60 of 192), respectively. The prevalence of IC infiltration and PD-L1 expression on IC were more strongly correlated with LCNEC than with SCLC (57.6% versus 23.3%, p < 0.01; 45.8% versus 22.5%, p < 0.01) and high nonsynonymous mutations (p = 0.05 and .04). PTEN loss was found in 9.5% of patients (18 of 189) and showed no correlation with PD-L1 expression. Progression-free survival was better in patients with IC infiltration than in those without IC infiltration (median 11.3 versus 6.8 months [p < 0.01]) and in patients with PD-L1 expression of IC1/2/3 than in those with expression of IC0 (median 11.3 versus 7.0 months [p = 0.03]).
These findings suggest that the PD-1/PD-L1 pathway is activated in the microenvironment of pulmonary high-grade neuroendocrine carcinoma and correlated with a higher mutation burden.
肺高级别神经内分泌癌的免疫微环境，包括程序性死亡配体 1（PD-L1）表达，尚未得到很好的描述。
根据免疫组化（IHC）结果，肿瘤细胞（TCs）和肿瘤浸润免疫细胞（ICs）上的 PD-L1 表达评分如下：TC0 和 IC0 定义为 PD-L1 表达小于 1%，TC1 和 IC1 为至少 1%但小于 10%，TC2 和 IC2 为 10%或更多但小于 50%，TC3 和 IC3 为 50%或更多。磷酸酶和张力蛋白同源物（PTEN）IHC 被评为缺失或保留表达。使用 Ion AmpliSeq 综合癌症面板（ThermoFisher Scientific，马萨诸塞州沃尔瑟姆）鉴定 409 个癌症相关基因所有编码外显子的突变。
共研究了 192 例大细胞神经内分泌癌（LCNEC）患者（n=72）和小细胞肺癌（SCLC）患者（n=120）。TCs 上 PD-L1 表达的患病率为 15.1%（29/192）。分别有 34.4%（66/192）和 31.3%（60/192）的患者存在 IC 浸润和 ICs 上的 PD-L1 表达。与 SCLC 相比，LCNEC 中 IC 浸润和 ICs 上 PD-L1 表达的患病率更高（57.6%对 23.3%，p<0.01；45.8%对 22.5%，p<0.01），并且与高非同义突变相关（p=0.05 和.04）。9.5%的患者（18/189）存在 PTEN 缺失，与 PD-L1 表达无相关性。与无 IC 浸润的患者相比，有 IC 浸润的患者的无进展生存期更好（中位 11.3 个月对 6.8 个月[p<0.01]），而 PD-L1 表达为 IC1/2/3 的患者的无进展生存期也优于 PD-L1 表达为 IC0 的患者（中位 11.3 个月对 7.0 个月[p=0.03]）。
这些发现表明，PD-1/PD-L1 通路在肺高级别神经内分泌癌的微环境中被激活，并与更高的突变负担相关。
