Abstract 4953: Differential expression of ICOS on circulating immune cells and tumor infiltrating lymphocytes in patient with solid tumors

Abstract

Abstract Background: The Inducible T-cell costimulator (ICOS/CD278) is upregulated during T cell activation and is an important regulator of the immune response against pathogens and cancer cells. When engaged by its ligand, the activation of ICOS signaling improves the survival of ICOS+ effector (TEff) and regulatory T cells (TReg). In addition, depending on the T cell subtypes expressing ICOS, activation of the signaling pathway induces the expression and secretion of either pro- (by TEff) or anti-inflammatory (by TReg) cytokines. ICOS has been reported to be upregulated in the tumor microenvironment (TME) of most tumor indications. However, the variability in ICOS expression levels on ICOS expressing T cells (TEff and TReg) and their relative abundance in different tumor types is still poorly understood. The aim of this study was to take advantage of multiple analytical platforms to assess the expression of ICOS on immune cells in the periphery and on tumor infiltrating lymphocytes (TILs) from cancers known to express high levels of ICOS, based on previous TCGA analyses. Methods: We analysed ICOS expression on peripheral blood mononuclear cell (PBMCs) and TILs by FACS, ChipcytometryTM and by single cell RNAseq. The analysis aimed to compare the expression of ICOS on different immune T cell subtypes. This comparison was performed on samples isolated from treatment naive non-small cell lung cancer (NSCLC) patients. In parallel, we established dual immunohistochemistry staining protocols supplemented by digital pathology to quantify and compare the expression of ICOS in the context of either FOXP3 or CD8 positive cells in NSCLC, gastric, esophageal, cervical, bladder and head and neck tumor samples. Results and conclusion: Using these approaches, we confirmed high ICOS expression in several solid tumor types. ICOS expression was also shown to be higher on immune cells in the TME compared to the periphery. Finally, ICOS expression was found to be more abundant on the surface of intratumoral TReg than on CD8+ T effector cells, confirming the data obtained in preclinical syngeneic tumor models (AACR2018 abstract #2792). Importantly, this work highlighted variability in the abundance and ratio of the different ICOS+ T cells subtypes (TEff and TReg) between different ICOSHigh tumors. Altogether, the variability in the intratumoral ratio of ICOS positive T cells observed in different tumor types could differentially affect their response to antibodies targeting ICOS. This work suggests that understanding the expression of ICOS in the context of different immune T cell subtypes may improve selection of patients with higher potential to respond to anti-ICOS therapies such as KY1044. Citation Format: Richard C. Sainson, Miha Kosmac, Rachael Kimber, Joana Carvalho, Gwenoline Bohris, Anil Thotakura, David Melvin, Matthew McCourt. Differential expression of ICOS on circulating immune cells and tumor infiltrating lymphocytes in patient with solid tumors [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 4953.