Abstract 5594: Inmune gene expression by nCounter in mucinous adenocarcinoma lung cancer

Abstract

Introduction: Although immune checkpoint inhibitors have become a standard of care for multiple cancer types; currently used biomarkers, such as PD-L1 expression, MSI or TMB, fail to identify all responders. In addition, little is known about markers of response to immunotherapy in some infrequent histological subtypes, such as mucinous adenocarcinoma of the lung. Gene expression signatures incorporating not only PD-L1 but also other immune modulators can have a better predictive power, particularly in these histological subtypes. Methods: A cohort of 165 baseline samples from with stage I-IV non-small cell lung cancer (NSCLC) patients was retrospectively analyzed, 55 stage I-IIIA mucinous adenocarcinomas (MA), 31 stage I-IIIA nonmucinous adenocarcinomas (NMA) and 79 stage IIIB-IV NMAs. RNA was extracted from FFPE tumor samples and the expression levels of a 7-gene immune signature (CD4, CD8A, FOXP3, GZMM, INFG, CD274 and PDCD1) were determined using a nCounter panel. Krustal-Wallis test was used for statistical comparisons. Results: No significant differences were observed in the expression levels of FOXP3 and PDCD1 (codifying forkhead box P3 and PD-1) between the three groups analyzed. In contrast, GZMM, IFNG and CD4 expression (codifying granzyme M, interferon gamma and CD4) was significantly higher in early stage MA compared to stage I-IIIA or stage IIIB-IV NMA. CD8A expression was significantly higher in early stage tumors, independently of the presence of mucinous component. In addition, the levels of CD274 mRNA (codifying PD-L1) were significantly higher in early stage MA compared to advanced stage NMA. Finally, among the stage I-IIIA MA, 27/55 (49%) were KRAS-mutant, but they did not show significant differences with KRAS-wt MAs in the expression of any of the genes tested. Conclusions: Mucinous adenocarcinoma of the lung shows a different pattern of expression of immune-related genes, which may influence response to immunotherapy. Citation Format: Ruth Román Lladó, Cristina Aguado Esteban, Ana Giménez-Capitán, Ueda Daisuke, Masaoki Ito, Yasuhiro Tsutani, Yoshihiro Miyata, Cristina Teixidó, Noemí Reguart, Morihito Okada, Sonia Rodríguez, Ariadna Balada, Erika Aldeguer, Santiago Viteri Ramirez, Maria Gonzalez Cao, Andrés Aguilar, Rafael Rosell, Miguel Angel Molina Vila. Inmune gene expression by nCounter in mucinous adenocarcinoma lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5594.