Abstract A40: Prevalence of TIGIT expression in normal tissues, inflammation, and cancer

Abstract

Introduction: TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is an immune checkpoint protein expressed on subsets of cytotoxic and regulatory T cells. TIGIT inhibiting drugs are currently being developed. The purpose of this study was to investigate the pattern of TIGIT expressing cells in normal tissues, inflammation and cancer. Methods: Monoclonal mouse antibodies were used for immunohistochemical TIGIT (Dianova, Hamburg, Germany) and PD1 (Abcam, Cambridge, UK, ab52587) analyses on formalin fixed paraffin embedded tissue sections from normal lymphatic tissues as well as selected inflammations and cancers. Results: In lymph nodes and tonsils, TIGIT positivity was seen in a large fraction of the germinal center T-cells. A high density of TIGIT positive T-cells also occurred in the marginal zone and in the interfollicular area. The analyses of selected inflammatory diseases revealed detectable TIGIT expression in a high proportion of T-lymphocytes in BCG induced cystitis and prostatitis, Hashimoto thyreoiditis, Lichen sclerosis of the penis, skin eczema, Crohn’s disease, and rheumatoid synovialitis. In all normal and inflammatory tissues, the pattern of TIGIT expression largely paralleled the pattern of PD1 expression. Three examples each of cancers types for which immune checkpoint inhibitors are already approved or extensively studied (melanoma, lung, kidney, bladder and colorectal cancer) were also analyzed. Here, the number of CD8 positive lymphocytes varied greatly between individual cases and the fraction of TIGIT and PD1 positive CD4 and CD8 positive lymphocytes varied considerably between cases. Conclusion: Expression of TIGIT is regularly seen in a large subset of T-cells and has a similar expression pattern as PD1. TIGIT’s frequent co-expression with PD1 in cytotoxic T-cells is consistent with TIGIT representing a clinically relevant druggable immune checkpoint regulator that potentially could be targeted in combination with PD1. Citation Format: Andrea Hinsch, Martina Kluth, Andreas M. Lubke, Anne Menz, Till Krech, Stefan Steurer, Doris Hoflmayer, Guido Sauter, Waldemar Wilczak, Kristine Fischer, Ronald Simon. Prevalence of TIGIT expression in normal tissues, inflammation, and cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A40.