MAIT cells regulate NK cell-mediated tumor immunity
| Autor: | Phillip K. Darcy, Angela Pizzolla, Rosemary Millen, Jessica Michie, James McCluskey, Timothy McCulloch, Junyun Lai, Jeffrey Y. W. Mak, Jack D Chan, Jasmine Li, Jane Oliaro, Amanda X. Y. Chen, Emma V. Petley, Paul A. Beavis, Imran G House, Kevin Sek, Hui-Fern Koay, Simon P. Keam, Robert G. Ramsay, Nicholas D. Huntington, Paul J Neeson, Dale I. Godfrey, Lauren Giuffrida, Melissa A. Henderson, Fernando Souza-Fonseca-Guimaraes, Amanda J Oliver, Andrew J. Freeman, Conor J. Kearney, Kirsten L. Todd, Magnus Zethoven, David P. Fairlie |
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| Rok vydání: | 2021 |
| Předmět: |
Science
Cell T cells General Physics and Astronomy Innate lymphoid cells Antineoplastic Agents Context (language use) Mucosal associated invariant T cell Biology Article Mucosal-Associated Invariant T Cells General Biochemistry Genetics and Molecular Biology Minor Histocompatibility Antigens Mice Antigen Immunity Cell Line Tumor Neoplasms medicine Animals Humans Neoplasm Metastasis Mice Knockout Immunity Cellular Multidisciplinary Histocompatibility Antigens Class I T-cell receptor General Chemistry Gene signature Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure Cell culture Cancer research Mucosal immunology Tumour immunology Cytokines |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment. Mucosal-associated invariant T (MAIT) cells facilitate anti-microbial responses, but their functions in cancer protection is unclear. Here the authors show that activated MAIT cells induce an IFN-γ transcriptome in natural killer (NK) cells and enhance NK-dependent anti-cancer immunity in mice, thereby hinting a new avenue for cancer therapy. |
| Databáze: | OpenAIRE |
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