Abstract SY09-01: The tumor immunity continuum as a framework for rational combinations

Abstract

Abstract The PD-L1/PD-1 pathway is emerging as a central axis for immune-based therapeutic strategies in the treatment of multiple cancers. While these therapies are defined by durable responses extending to impressive overall survival improvement, this clinical benefit is limited to a few. We utilized gene signature analysis of cell subsets associated with the TME and molecular classification of disease using whole transcriptome analysis, PD-L1 IHC, CD8 IHC and tumor mutational load to identify signatures associated with immune response to atezolizumab (ati-PDL1) therapy from large Phase II trials and describe signatures associated with immune escape. Namely, we demonstrate that a preexisting immune response associated with inflamed tumors is highly predictive of clinical benefit to checkpoint inhibition. In addition, we describe both histological and molecular phenotypes associated with immune escape. The biological drivers of PD-L1 expression on tumor cells and tumor infiltrating immune cells will be presented. Using the lessons learned from human tumor immunology, we propose the concept of the tumor immunity continuum as a framework to expand the patient pool that derive long-term clinical benefit by harnessing their immune system. Citation Format: Priti S. Hegde. The tumor immunity continuum as a framework for rational combinations. [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 SY09-01.