Abstract 3993: Programmed cell death ligand-1 (PD-L1) and CD8 expression profiling identifies an immunologic subtype of pancreatic ductal adenocarcinomas with favorable survival

Abstract

Abstract Unselected cases of pancreatic adenocarcinoma (PDAC) have not shown clinical benefit from single agent immune checkpoint therapy, but a subset of PDAC are known to upregulate pathways involved in acquired immune suppression. Further delineation of immunologic subtypes of PDAC is key to smarter trial designs and progress toward improved immunotherapy strategies. To accomplish this, we first employed clinical survival and RNA expression data from 155 patients in The Cancer Genome Atlas (TCGA) to investigate the relationship between immune modulating checkpoints and immune subset marker, CD8A, and their impact on survival in PDAC patients. Among the markers explored, overexpression of PD-L1 (HR=2.55, p=0.001) and IDO1 (HR=2.24, p<0.01) were individually associated with poor survival. PD-L1 expression was not significantly associated with stage or tumor mutational burden of the PDACs. While CD8A expression alone was not correlated with survival, stratifying the analysis based on PD-L1 and CD8 expression identified a subtype characterized by low PD-L1 and high CD8A with favorable survival (p=0.004). Similarly, the combination of low IDO1 and high CD8A expression was associated with favorable survival (p=0.038). We further extended these observations using an independent PDAC cohort of 33 patients from our institution via immunohistochemistry, again observing that low PD-L1 / high CD8 subtype associates with positive prognosis (p=0.021). Although PDAC is regarded as a poorly immunogenic cancer type, these findings infer that baseline T cell infiltration into PDAC is a feature of long term survival and highlights the importance of developing future immunotherapeutic strategies based on data-supported biomarkers to refine patient selection. Citation Format: Won Jin Ho, Ludmila Danilova, Qingfeng Zhu, Teena Vithayathil, Ana De Jesus-Acosta, Nilo Azad, Daniel Laheru, Elana Fertig, Robert Anders, Elizabeth Jaffee, Mark Yarchoan. Programmed cell death ligand-1 (PD-L1) and CD8 expression profiling identifies an immunologic subtype of pancreatic ductal adenocarcinomas with favorable survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3993.