Abstract 5140: PD-L1 expression and its relationship with other driver genes in non-small cell lung cancer (NSCLC)
Authors: Liyan Jiang, Xinying Su, Tianwei Zhang, Xiaolu Yin, Meizhuo Zhang, Haihua Fu, Hulin Han, Yun Sun, Lili Dong, Jialin Qian, Yanhua Xu, Xuan Fu, Paul Gavine, Yanbin Zhou, Tian Kun, Jiaqi Huang, Haiyi Jiang, Yihong Yao, Baohui Han, Yi Gu
Journal: Cancer Research (2016)

Abstract Aims: In order to understand the potential patient population who could benefit from anti PD-1/PD-L1 mono or combinational therapies, this study aimed to profile a panel of immune-mediated therapy for cancer (IMT-C) related biomarkers (CD8, PD-1, PD-L1 and CTLA-4) and molecular targeted therapy biomarkers (EGFRmut, KRASmut, ALK, ROS1 and MET) in NSCLC patients. Methods: Tumor samples from 356 Chinese NSCLC patients including 191 adenocarcinomas (AD) and 142 squamous carcinomas (SCC) were analyzed in this study. There were 221 early stage (I to IIIa) and 113 late stage (IIIb and IV) patients. PD-L1, PD-1, CTLA-4 and MET expression were detected using immunohistochemical (IHC) staining on formalin fixed paraffin embedded (FFPE) tissues. PD-L1 and CD8 expression were also simultaneously observed using a dual-color immunofluorescence (IF) assay. EGFR and KRAS mutations were detected by sequencing analysis. ALK and ROS1 gene rearrangements were defined by break-apart FISH assays, and MET gene amplification was also detected using a FISH assay. Results: Among 356 NSCLC patient samples, 145 (40.7%) had PD-L1 positive staining on ≥5% tumor cells (TC). The PD-L1 positive rate on TC was significantly higher in SCC than in AD (47.9% vs 34.0%, p = 0.011). In AD patients, PD-L1 expression was significantly elevated in males (p = 0.0059), smokers (p = 0.0003), higher tumor grade (p&amp;lt;0.00001) and late stage (p = 0.0009) patients. In addition, we found that 53.1% (113/213) patient samples had PD-L1 expression on tumor infiltrating immune cells (IC). Again, the PD-L1 positive rate on IC was higher in SCC than in AD (66.0% vs 36.6%, p&amp;lt;0.0001). Comparing the two cell types, 70% of the total cases had consistent PD-L1 staining status (positive or negative) on TC and tumor infiltrating IC (p&amp;lt;0.0001). Among 117 cases detected using dual-color IF, all had CD8 positive lymphocytes in the tumor samples while 54 cases were PD-L1 TC positive. The most interesting finding was CD8 and PD-L1 double stained lymphocytes were mainly located in the tumor center in 37 out of 42 cases. Furthermore, combined analysis of the eight biomarkers studied in this cohort of NSCLC samples showed that tumor PD-L1 positive staining (on ≥5% tumor cells) had overlaps with the other NSCLC driver genes’ alterations in 28% of SCC and 69% of AD samples. Conclusion: This study showed almost half of NSCLC patients have PD-L1 positive expression on TC, which to some extent overlaps with EGFR/KRAS mut, ALK/ROS1 rearrangement and MET alteration. As a potential patient selection biomarker, the PD-L1 positive prevalence in NSCLC TC and/or tumor infiltrating IC provides a strong evidence for PD-1/PD-L1 immune therapy in single agent or in combination with the molecular targeted agents. Furthermore, CD8+ lymphocyte’ infiltration in the tumor center and its PD-L1 expression status might also be considered as part of patient selection biomarker strategy. Citation Format: Liyan Jiang, Xinying Su, Tianwei Zhang, Xiaolu Yin, Meizhuo Zhang, Haihua Fu, Hulin Han, Yun Sun, Lili Dong, Jialin Qian, Yanhua Xu, Xuan Fu, Paul Gavine, Yanbin Zhou, Tian Kun, Jiaqi Huang, Haiyi Jiang, Yihong Yao, Baohui Han, Yi Gu. PD-L1 expression and its relationship with other driver genes in non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5140.