TIGIT expressing CD4+T cells represent a tumor-supportive T cell subset in chronic lymphocytic leukemia
| Autor: | Kemal Catakovic, Franz Josef Gassner, Christoph Ratswohl, Nadja Zaborsky, Stefan Rebhandl, Maria Schubert, Markus Steiner, Julia Christine Gutjahr, Lisa Pleyer, Alexander Egle, Tanja Nicole Hartmann, Richard Greil, Roland Geisberger |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | OncoImmunology, Vol 7, Iss 1 (2018) |
| Druh dokumentu: | article |
| ISSN: | 2162-402X 2162402X |
| DOI: | 10.1080/2162402X.2017.1371399 |
| Popis: | While research on T cell exhaustion in context of cancer particularly focuses on CD8+ cytotoxic T cells, the role of inhibitory receptors on CD4+ T-helper cells have remained largely unexplored. TIGIT is a recently identified inhibitory receptor on T cells and natural killer (NK) cells. In this study, we examined TIGIT expression on T cell subsets from CLL patients. While we did not observe any differences in TIGIT expression in CD8+ T cells of healthy controls and CLL cells, we found an enrichment of TIGIT+ T cells in the CD4+ T cell compartment in CLL. Intriguingly, CLL patients with an advanced disease stage displayed elevated numbers of CD4+ TIGIT+ T cells compared to low risk patients. Autologous CLL-T cell co-culture assays revealed that depleting CD4+ TIGIT+ expressing T cells from co-cultures significantly decreased CLL viability. Accordingly, a supportive effect of TIGIT+CD4+ T cells on CLL cells in vitro could be recapitulated by blocking the interaction of TIGIT with its ligands using TIGIT-Fc molecules, which also impeded the T cell specific production of CLL-prosurvival cytokines. Our data reveal that TIGIT+CD4+T cells provide a supportive microenvironment for CLL cells, representing a potential therapeutic target for CLL treatment. |
| Databáze: | Directory of Open Access Journals |
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