Abstract 2142: High variability of TIGIT expression in Hodgkin's lymphoma

Abstract

Abstract Hodgkin's lymphoma (HL) is characterized by a high background of inflammatory cells which play an important role for the pathogenesis of the disease. 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 in the T cell background surrounding malignant cells including Hodgkin cells, Reed-Sternberg cells and histiocytic cells, a microenvironment (ME) tissue microarray (TMA) was constructed from tissue punches measuring 2 mm in diameter obtained from formalin-fixed tissue samples of Hodgkin lymphoma lymph nodes (n=40) and normal human tonsil (n=2) as a reference. The ME-TMA was stained with brightfield and multiplex fluorescence immunohistochemistry (IHC) in order to evaluate expression levels of TIGIT and PD-1 as well as standard lymphocyte markers (CD8, CD4, FOXP3) in the lymphocytic background. TIGIT and PD-1 expression was found in all (100%) analyzed HL samples. In general, TIGIT localized to the same cells as PD-1. IHC based identification of T cell subtypes revealed TIGIT and PD-1 expression on CD8+ cytotoxic T cells, CD4+ helper T cells and FOXP3+ regulatory T cells. Strikingly, expression levels of TIGIT and PD-1 were highly variable among the analyzed samples irrespective of the histological subtype of HL. Interestingly, highest levels of both proteins were found in one sample of nodular lymphocytic-predominant HL (NLPHL). The high variability of TIGIT and PD-1 expression was also independent from the T cell subtype. HL with high TIGIT/PD-1 expression on CD8 positive cells sometimes showed low TIGIT/PD-1 expression on CD4 or FOXP3 positive T cells and vice versa. However, the T cell subtypes differed with respect to the TIGIT:PD-1 ratio. In the majority of analyzed HL, FOXP3+ regulatory T cells expressed higher levels of TIGIT than of PD-1. This was different for CD8+ and CD4+ cells, where similar fractions of HL showed either more TIGIT as PD-1, or more PD-1 as TIGIT, or comparable levels of both receptors. In conclusion, TIGIT (and PD-1) expression is highly variable between patients with Hodgkin's lymphoma. TIGIT may play a particularly important role in FOXP3 regulatory T cells in the lymphocytic background. Citation Format: Ronald Simon, Niclas C. Blessin, 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. High variability of TIGIT expression in Hodgkin's lymphoma [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 2142.