| Literature DB >> 25680274 |
Chamutal Gur1, Yara Ibrahim2, Batya Isaacson3, Rachel Yamin3, Jawad Abed2, Moriya Gamliel3, Jonatan Enk3, Yotam Bar-On3, Noah Stanietsky-Kaynan3, Shunit Coppenhagen-Glazer2, Noam Shussman4, Gideon Almogy4, Angelica Cuapio5, Erhard Hofer5, Dror Mevorach6, Adi Tabib6, Rona Ortenberg7, Gal Markel7, Karmela Miklić8, Stipan Jonjic8, Caitlin A Brennan9, Wendy S Garrett10, Gilad Bachrach11, Ofer Mandelboim12.
Abstract
Bacteria, such as Fusobacterium nucleatum, are present in the tumor microenvironment. However, the immunological consequences of intra-tumoral bacteria remain unclear. Here, we have shown that natural killer (NK) cell killing of various tumors is inhibited in the presence of various F. nucleatum strains. Our data support that this F. nucleatum-mediated inhibition is mediated by human, but not by mouse TIGIT, an inhibitory receptor present on all human NK cells and on various T cells. Using a library of F. nucleatum mutants, we found that the Fap2 protein of F. nucleatum directly interacted with TIGIT, leading to the inhibition of NK cell cytotoxicity. We have further demonstrated that tumor-infiltrating lymphocytes expressed TIGIT and that T cell activities were also inhibited by F. nucleatum via Fap2. Our results identify a bacterium-dependent, tumor-immune evasion mechanism in which tumors exploit the Fap2 protein of F. nucleatum to inhibit immune cell activity via TIGIT.Entities:
Mesh：
Substances：
Year: 2015 PMID： 25680274 PMCID： PMC4361732 DOI： 10.1016/j.immuni.2015.01.010
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745