Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer

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.