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

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...

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Detalles Bibliográficos
Autores principales: 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., Wittmer, Corinna, Jacobsen, Frank, Burandt, Eike-Christian, Steurer, Stefan, Wilczak, Waldemar, Hinsch, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348838/
https://www.ncbi.nlm.nih.gov/pubmed/30733837
http://dx.doi.org/10.1155/2019/5160565
Descripción
Sumario: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.