Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, Università Degli Studi di Padova, Padova, Italy.
Eur J Cancer. 2018 Sep;101:191-200. doi: 10.1016/j.ejca.2018.06.023. Epub 2018 Aug 1.
The prognosis of small-cell lung cancer (SCLC) is dismal and new effective therapies are needed. Immunotherapy looks promising, but no molecular predictive markers are currently available, and data on immune microenvironment are very limited.
We retrospectively analysed 104 SCLC cases. Immunohistochemistry evaluation of PD-L1 was performed both on tumour cells (TCs) and on tumour-infiltrating immune cells (TIICs) by using anti-PD-L1 22C3 antibody (DAKO) and categorised by using 1% as cut-off point. Tumour-infiltrating lymphocytes (TILs) were characterised by using anti-CD8 and anti-FOXP3 antibodies. Semi-quantitative score was used and categorised as positive versus negative/low. The relation of molecular markers with prognosis and with clinical variables was evaluated.
The analysis included 66 stage I-III patients (48 surgically resected, 18 treated with radical-intent chemoradiotherapy) and 38 metastatic cases. In the overall study population, PD-L1 was expressed on TCs and TIICs in 25% and 40% of cases, respectively. The proportion of PD-L1-positive cases was significantly higher in stage I-III versus metastatic patients (32% versus 13%, p: 0.034 for TCs; 51.5% versus 21% for TIICs, p: 0.002). CD8- and FOXP3-positive TILs were present in 59% and 72% of samples, respectively. The presence of FOXP3-TILs was associated with improved prognosis among non-metastatic patients, with a hazard ratio for survival of 0.32 (95% confidence interval [CI]: 0.16-0.7, p: 0.006) for univariate analysis, and 0.37 (95% CI: 0.17-0.81, p: 0.013) for multivariate analysis.
Immune contexture of SCLC may differ according to stage. The presence of FOXP3-positive TILs is a potential prognostic marker for stage I-III SCLCs and warrants further investigation.
小细胞肺癌（SCLC）的预后较差，需要新的有效治疗方法。免疫疗法前景广阔，但目前尚无分子预测标志物，且免疫微环境数据非常有限。
我们回顾性分析了 104 例 SCLC 病例。使用抗 PD-L1 22C3 抗体（DAKO）对肿瘤细胞（TCs）和肿瘤浸润免疫细胞（TIICs）进行 PD-L1 的免疫组织化学评估，并使用 1%作为截断值进行分类。使用抗 CD8 和抗 FOXP3 抗体对肿瘤浸润淋巴细胞（TILs）进行特征描述。使用半定量评分，并分为阳性与阴性/低表达。评估了分子标志物与预后及临床变量的关系。
该分析包括 66 例 I-III 期患者（48 例接受手术切除，18 例接受根治性放化疗）和 38 例转移性病例。在整个研究人群中，TCs 和 TIICs 上分别有 25%和 40%的病例表达 PD-L1。I-III 期患者 PD-L1 阳性病例的比例明显高于转移性患者（TCs：32%比 13%，p：0.034；TIICs：51.5%比 21%，p：0.002）。FOXP3-TILs 在 59%和 72%的样本中存在。在非转移性患者中，FOXP3-TILs 的存在与预后改善相关，单因素分析的生存风险比为 0.32（95%可信区间[CI]：0.16-0.7，p：0.006），多因素分析的风险比为 0.37（95%CI：0.17-0.81，p：0.013）。
SCLC 的免疫微环境可能根据分期而不同。FOXP3 阳性 TILs 的存在是 I-III 期 SCLC 的潜在预后标志物，值得进一步研究。
