Abstract 696: Patterns of TIGIT expression in normal lymphatic tissue, inflammation and cancer
Authors: Blessin Niclas C. , Simon Ronald , Kluth Martina , Fischer Kristine , Hube-Magg Claudia , Li Wenchao , Makrypidi-Fraune Georgia , Wellge Björn , Mandelkow Tim , Debatin Nicolaus F. , Sauter Guido , Wilczak Waldemar , Hinsch Andrea 
Published: August 2018

Abstract
T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory immune checkpoint receptor and a putative target for novel immune therapies. To study patterns of TIGIT expression, “microenvironment tissue microarrays” containing 4mm tissue spots were constructed from lymph nodes of healthy (n=3) and HIV infected individuals (n=2), normal tonsils (n=3), Hashimoto thyroiditis (n=10), sarcoidosis (n=10), lichen sclerosus (n=2), IgG4-pancreatitis (n=2), rheumatoid arthritis (n=2) colorectal (n=5) and lung cancers (n=2) and analyzed for expression of TIGIT, PD-1 and standard lymphocyte markers by brightfield and multiplex fluorescence immunohistochemistry. TIGIT expression was seen in CD8+ cytotoxic T cells, CD4+ T-helper cells, FOXP3+ regulatory T cells and in NK cells, but not in CD11c+ dendritic cells, CD68+ macrophages and CD20+ B lymphocytes. TIGIT expression paralleled that of PD-1. More than 70% of TIGIT positive cells were PD-1 positive and more than 90% of the PD-1 positive cells were TIGIT positive. Expression of both proteins varied between different tissue compartments. TIGIT expression in tonsil gradually increased from the interfollicular area over the marginal/mantle zone to the germinal center in all T cell subtypes. Stronger expression of TIGIT and PD-1 than in tonsil germinal centers (2-3 fold) was only found in Hashimoto thyroiditis germinal centers. Marked location specific variations were also seen in other inflammatory diseases and in cancers. In general, TIGIT and PD-1 expression was higher in lymphocyte-dense compartments, such as areas of lymphocytic infiltration in sarcoidosis, IgG4 pancreatitis or rheumatoid arthritis, than in areas containing fewer and scattered lymphocytes. In lung and colorectal cancers, the density of TIGIT and PD-1 expressing T cells was highest at the invasion front. Also, the TIGIT and PD-1 expression levels were typically stronger in tumor adjacent stromal CD8+ cells than in tumor infiltrating CD8+ cells. In conclusion, TIGIT is regularly expressed in a large subset of T cells. The variable expression levels of TIGIT and PD-1 between cell types and tissue compartments illustrates the high complexity of immune response. The frequent co-expression of TIGIT and PD-1 may offer an opportunity for co-targeting these proteins with checkpoint inhibitor drugs.
Citation Format: Niclas C. Blessin, Ronald Simon, Martina Kluth, Kristine Fischer, Claudia Hube-Magg, Wenchao Li, Georgia Makrypidi-Fraune, Björn Wellge, Tim Mandelkow, Nicolaus F. Debatin, Guido Sauter, Waldemar Wilczak, Andrea Hinsch. Patterns of TIGIT expression in normal lymphatic tissue, inflammation and cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 696.