Background: Programmed death-ligand 1 (PD-L1) is widely used biomarker for the response prediction of immune checkpoint inhibitors, but its usefulness has been challenged. MYC, a transcriptional factor which is overexpressed in various cancers, plays critical roles in preventing immune cells from attacking tumor cells by inducing PD-L1 expression. We evaluated that MYC expression is positively related that of PD-L1 in non-small cell lung cancer (NSCLC) clinical specimens and that it has potential as a predictor of response to immune checkpoint inhibitors in NSCLC.
Methods: Eighty-four cases who were diagnosed as NSCLC and underwent surgical resection were evaluated by immunohistochemistry (IHC). PD-L1 expression was evaluated by FDA-approved PD-L1, 22C3 PharmDxTM protocol using the Dako Automated Link 48 platform at Clarient Diagnostic Services, Inc (Aliso Viejo, CA, USA). Its expression was determined by using Tumor Proportion Score (TPS), which is the percentage of viable tumor cells showing partial or complete membrane staining. If TPS >= 50% of the viable tumor cells exhibit membrane staining at any intensity, it was considered positive. IHC of MYC was performed using anti-c-MYC antibody [Y69] (ab32072, Abcam, USA) and its expression was evaluated by scoring system using product of nuclear staining intensity and percentage of positive cells.
Results: When MYC cDNA was transfected into KRAS-dependent lung cancer cell lines that did not express both MYC and PD-L1, the protein expression and mRNA of PD-L1 were induced in a dose-dependent manner. On the other hands, knockdown of MYC with siRNA inhibited protein expression and mRNA indicating MYC regulates PD-L1 at transcriptional level. Of 84 NSCLC tumor tissues, PD-L1 was expressed in 14 (16.7%) and MYC in 30 (35.7%) cases. Dual positive patients were 9 (10.7%) and dual negative patients were 49 (58.3%). When the relationship between PD-L1 and MYC expression was evaluated, significant positive correlation was observed between PD-L1 and MYC expression (γ=0.267, P=0.014). Dual positive patients showed significantly shorter disease free survival (16.1 vs. 62.5 months, P=0.004) and overall survival (24.9 vs. 70.9 months, P=0.002) than dual negative patients.
Conclusion: MYC expression correlates with PD-L1 expression in the NSCLC and the patients with overexpression of both MYC and PD-L1 showed significantly poor survival. This suggest that it is worth of investigation of MYC expression as a surrogate predictive marker for treatment of immune checkpoint inhibitors in NSCLC.
Citation Format: Eun Young Kim, Arum Kim, Se Kyu Kim, Yoon Soo Chang. MYC expression correlates with PD-L1 expression and related poor clinical outcome in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4719. doi:10.1158/1538-7445.AM2017-4719