D'Arcangelo Manolo, D'Incecco Armida, Ligorio Claudia, Damiani Stefania, Puccetti Maurizio, Bravaccini Sara, Terracciano Luigi, Bennati Chiara, Minuti Gabriele, Vecchiarelli Silvia, Landi Lorenza, Milesi Marina, Meroni Alberto, Ravaioli Sara, Tumedei Maria Maddalena, Incarbone Matteo, Cappuzzo Federico
AUSL della Romagna, Department of Oncology-Hematology, Ravenna, Italy.
University Hospital of Siena, Medical Oncology and Immunotherapy, Center for Immuno-Oncology, Siena, Italy.
Oncotarget. 2019 Jan 15;10(5):561-572. doi: 10.18632/oncotarget.26529.
For several years non-small cell lung cancer (NSCLC) has been considered non-immunogenic. Recent advances in antitumor immunity brought to the discovery of checkpoints that modulate immune response against cancer. One of them is programmed death receptor 1 (PD-1) and its ligand (PD-L1). Although PD-L1 expression seems predictive of response to anti-PD-1/PD-L1 agents, its prognostic value is unclear. In this study we investigated the prognostic value of PD-L1 expression and its correlation with clinical-pathological characteristics in a cohort of surgically resected NSCLC.
PD-L1 expression was evaluated in 289 surgically resected NSCLC samples by immunohistochemistry. Our cohort included patients not exposed to adjuvant chemotherapy. PD-L1 status was defined as: 1) PD-L1 high (tumor proportion score, TPS≥50%), PD-L1 low (TPS 1-49%), PD-L1 negative (TPS<1%); 2) PD-L1 positive (TPS≥50%) and negative (TPS<50%); 3) as a continuous variable.
Patients were mostly males (79%), former or current smokers (81%), with a median age of 67 years, non-squamous histology (67.5%) and high-grade tumors (55%). PD-L1 tumors were 18.7%. There was no significant association with sex, age, smoking status and histology. A strong correlation between high PD-L1 expression and tumor grade was detected. The difference in median OS in the different groups of patients was not statistically significant.
PD-L1 is not prognostic in surgically resected NSCLC. The association with tumor differentiation suggests that grading could represent an easy-to-assess tool for selecting subjects potentially sensitive to immunotherapy warranting further investigations.
多年来，非小细胞肺癌（NSCLC）一直被认为是无免疫原性的。抗肿瘤免疫的最新进展带来了对调节抗癌免疫反应的检查点的发现。其中之一是程序性死亡受体1（PD-1）及其配体（PD-L1）。尽管PD-L1表达似乎可预测对抗PD-1/PD-L1药物的反应，但其预后价值尚不清楚。在本研究中，我们调查了手术切除的NSCLC队列中PD-L1表达的预后价值及其与临床病理特征的相关性。
通过免疫组织化学评估289例手术切除的NSCLC样本中的PD-L1表达。我们的队列包括未接受辅助化疗的患者。PD-L1状态定义为：1）PD-L1高表达（肿瘤比例评分，TPS≥50%），PD-L1低表达（TPS 1-49%），PD-L1阴性（TPS<1%）；2）PD-L1阳性（TPS≥50%）和阴性（TPS<50%）；3）作为连续变量。
患者大多为男性（79%），既往或当前吸烟者（81%），中位年龄67岁，非鳞状组织学（67.5%）和高级别肿瘤（55%）。PD-L1肿瘤为18.7%。与性别、年龄、吸烟状态和组织学无显著关联。检测到高PD-L1表达与肿瘤分级之间存在强相关性。不同组患者的中位总生存期差异无统计学意义。
PD-L1在手术切除的NSCLC中无预后价值。与肿瘤分化的关联表明，分级可能是一种易于评估的工具，用于选择可能对免疫治疗敏感的受试者，值得进一步研究。
