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- Title
Patterns of TIGIT Expression in 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.; Höflmayer, Doris; Lennartz, Maximilian; Sauter, Guido; Izbicki, Jakob R.; Minner, Sarah; Büscheck, Franziska; Uhlig, Ria; Dum, David; Krech, Till; Luebke, Andreas M.
- Abstract
TIGIT is an inhibitory immune checkpoint receptor and a putative target for novel immune therapies. Here, we analysed two different types of tissue microarrays of healthy lymphatic and various inflamed tissues, colorectal and lung cancers, as well as >1700 tumour samples from 86 different tumour entities for TIGIT and/or PD-1 by bright field and/or multiplex fluorescence immunohistochemistry. TIGIT was detected in CD8+ cytotoxic T cells, CD4+ T helper cells, FOXP3+ regulatory T cells, and 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+ cells were PD-1+, and more than 90% of the PD-1+ cells were TIGIT+. Expression varied between different tissue compartments. TIGIT expression in tonsil gradually increased from the interfollicular area over the marginal/mantle zone to the germinal centre in all T cell subtypes. In inflammatory diseases, the strongest expression of TIGIT/PD-1 was found in Hashimoto thyroiditis. TIGIT+ lymphocytes were seen in all 86 different tumour entities with considerable high variability of TIGIT positivity within and between different cancer entities. Particularly, high densities of TIGIT+ lymphocytes were, for example, seen in squamous cell cancers of various origins. In summary, the variable expression levels of TIGIT and PD-1 in cell types and tissue compartments illustrate the high complexity of immune microenvironments. The high frequency of TIGIT (and PD-1) expressing lymphocytes in cancers highlights considerable opportunities for cotargeting with checkpoint inhibitors.
- Subjects
LYMPHOID tissue; INFLAMMATION; T cells; IMMUNOHISTOCHEMISTRY; AUTOIMMUNE thyroiditis
- Publication
Disease Markers, 2019, p1
- ISSN
0278-0240
- Publication type
Article
- DOI
10.1155/2019/5160565