Yang Ching-Yao, Lin Mong-Wei, Chang Yih-Leong, Wu Chen-Tu, Yang Pan-Chyr
Department of Internal Medicine, Taiwan, ROC; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan, ROC.
Department of Surgery, Taiwan, ROC; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan, ROC.
Eur J Cancer. 2016 Apr;57:91-103. doi: 10.1016/j.ejca.2015.12.033. Epub 2016 Feb 21.
Programmed cell death-ligand 1 (PD-L1) is expressed in a subgroup of lung cancer that may benefit from immunotherapy. The interaction between PD-L1 expression and tumour infiltrating lymphocytes (TIL) remains poorly understood. This study investigated the expression of PD-L1 in surgically resected stage I pulmonary squamous cell carcinoma (SqCC) and correlated it with TILs in tumour microenvironments, common driver mutations, and clinical outcomes.
One hundred and five patients with surgically resected stage I squamous cell carcinoma were examined. Paraffin-embedded tumour sections were stained with PD-L1 antibody. Tumours with moderate-to-strong membrane staining in ≥ 5% of tumour cells were scored as positive for PD-L1 expression. The driver mutation epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) were examined by direct sequencing, while anaplastic lymphoma kinase (ALK), phosphoinositide 3-kinase catalytic alpha (PI3KCA), and fibroblast growth factor receptor 1 (FGFR1) were analysed by immunohistochemistry. The correlations of PD-L1 expression with each subtype of TIL, driver mutations, clinicopathologic parameters, and clinical outcomes were analysed.
There was positive PD-L1 expression in 56.2% (59/105) of patients. PD-L1 expression was not associated with the common clinicopathologic features and mutations of EGFR, KRAS, BRAF, ALK, PI3KCA, and FGFR1. As regards TILs composition, tumour PD-L1 expression was significantly associated with increased tumour epithelial CD8+ T cells and stromal CD4+ T cells. Otherwise, PD-L1 (+) tumour cells were negatively correlated with PD-L1 (+) immune cells within tumour stroma. By multivariate analysis, tumour PD-L1 expression and increased CD4+ T cell infiltrations in the tumour stroma were independent predictors of better overall survival and had a trend of better disease-free survival.
PD-L1 expression is associated with a favourable immune microenvironment in stage I pulmonary SqCC and correlates with better clinical outcome.
程序性细胞死亡配体1（PD-L1）在肺癌的一个亚组中表达，该亚组可能从免疫治疗中获益。PD-L1表达与肿瘤浸润淋巴细胞（TIL）之间的相互作用仍了解甚少。本研究调查了手术切除的I期肺鳞状细胞癌（SqCC）中PD-L1的表达，并将其与肿瘤微环境中的TIL、常见驱动基因突变及临床结局相关联。
对105例手术切除的I期鳞状细胞癌患者进行检查。石蜡包埋的肿瘤切片用PD-L1抗体染色。肿瘤细胞中≥5%呈中度至强膜染色的肿瘤被判定为PD-L1表达阳性。通过直接测序检测驱动基因突变表皮生长因子受体（EGFR）、 Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）和v-raf鼠肉瘤病毒癌基因同源物B（BRAF），而通过免疫组织化学分析间变性淋巴瘤激酶（ALK）、磷酸肌醇3激酶催化亚基α（PI3KCA）和成纤维细胞生长因子受体1（FGFR1）。分析PD-L1表达与各亚型TIL、驱动基因突变、临床病理参数及临床结局的相关性。
56.2%（59/105）的患者PD-L1表达呈阳性。PD-L1表达与EGFR、KRAS、BRAF、ALK、PI3KCA和FGFR1的常见临床病理特征及突变无关。关于TILs组成，肿瘤PD-L1表达与肿瘤上皮CD8+T细胞和基质CD4+T细胞增加显著相关。此外，PD-L1（+）肿瘤细胞与肿瘤基质内的PD-L1（+）免疫细胞呈负相关。通过多变量分析，肿瘤PD-L1表达和肿瘤基质中CD4+T细胞浸润增加是总生存期更好的独立预测因素，且有疾病无进展生存期更好的趋势。
PD-L1表达与I期肺SqCC中良好的免疫微环境相关，并与更好的临床结局相关。
