In:
Disease Markers, Hindawi Limited, Vol. 2019 ( 2019-01-10), p. 1-13
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.
Type of Medium:
Online Resource
ISSN:
0278-0240
,
1875-8630
DOI:
10.1155/2019/5160565
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2019
detail.hit.zdb_id:
2033253-1
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