Abstract 497: Characterization of TIGIT expression using MultiOmyxTM hyperplexed immunofluorescence assay in solid tumors

Abstract

Abstract TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a recently identified immune-receptor that is expressed on T cells, natural killer (NK) cells and NKT cells. TIGIT has emerged as an important coinhibitory receptor. TIGIT expression on CD8+ tumor infiltrating lymphocytes (TILs) has been shown to be upregulated in solid cancers such as melanoma, colon cancer, and NSCLC and have been associated with a dysfunctional phenotype in TILs. TIGIT can also be activated on a subset of Regulatory T cells (Tregs) and may be critical in driving CD8+ T cell dysfunction. A second mechanism in which TIGIT inhibits immunosurveillance is through both competition and direct inhibition of CD226, impairing its ability to activate immunosurveillance. TIGIT has also been reported to inhibit T cell responses indirectly by triggering CD155 expression in dendritic cells (DCs), thereby preventing DC maturation. These findings render the TIGIT pathway as an attractive candidate for cancer immunotherapy In this study, we seek to use MultiOmyx hyperplexed immunofluorescence (IF) assay to exploit this new pathway and characterize the TIGIT expression in a total of 20 melanoma and NSCLC samples. The cancer FFPE slides will be stained with a 13-marker panel including TIGIT, CD226, CD155, CD3, CD4, CD8, FOXP3, CD56, CD45, CD11b, CD11c, PD1, LAG3, TIM3 and PanCK. This panel will enable the detection of TIGIT, CD226 and CD115 expression in the Melanoma and NSCLC samples. The TIGIT expression will be further characterized on different TILs including CD4+ helper T cells, CD8+ cytotoxic T cells, Tregs and NK cells. Using the MultiOmyx proprietary algorithm, we can quantify different subtypes of TIGIT expressing cells and measure the distance of different TIGIT expressing cells to the tumor. Increased expression of TIGIT and PD1 has been demonstrated in NSCLC and melanoma. Moreover, TIGIT+ Tregs have been reported to upregulate TIM-3 expression in mice tumor models. In this study, we will also evaluate the expression of TIGIT in conjunction with other coinhibitory receptors such as PD1, LAG3 and TIM3. The percentage of TILs that co-express TIGIT/PD1, TIGIT/LAG3 and TIGIT/TIM3 will be quantified and analyzed. Leveraging TIGIT in combination with other immune therapy may achieve more robust clinical outcomes. There are currently multiple phase I clinical trials using TIGIT monoclonal antibody (for instance, BMS-986207 by Bristol-Myers Squibb and MTIG7192A by Genetech) in combination with anti PD1/PDL1 antibodies in solid tumors. Our data can help provide more insight into how TIGIT modulate antitumor immunity in melanoma and NSCLC tumors. And the findings in this study can also be used to understand the synergistic effects between TIGIT and other coinhibitory receptors and help identify the additional opportunity for combination immunotherapy using checkpoint inhibitors. Citation Format: Qingyan Au, Arezoo Hanifi, Erinn Parnell, Judy Kuo, Eric Leones, Flora Sahafi, Kathy Pham, RaghavKrishna Padmanabhan, Nicholas Hoe, Josette William. Characterization of TIGIT expression using MultiOmyxTM hyperplexed immunofluorescence assay in 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 497.