Loss of type I IFN responsiveness impairs natural killer cell antitumor activity in breast cancer.

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Abstrakt

Tytuł:: Loss of type I IFN responsiveness impairs natural killer cell antitumor activity in breast cancer.
Autorzy:: Zanker DJ; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Owen KL; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Baschuk N; Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.
Spurling AJ; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.
Parker BS; Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia. .; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia. .; Department of Biochemistry and Genetics, La Trobe Institute from Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia. .
Źródło:: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2021 Aug; Vol. 70 (8), pp. 2125-2138. Date of Electronic Publication: 2021 Jan 15.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: Berlin : Springer Verlag
Original Publication: Berlin ; New York, NY : Springer International, c1982-
MeSH Terms:: Breast Neoplasms/*immunology
Interferon Type I/*immunology
Killer Cells, Natural/*immunology
Animals ; Carcinogenesis/immunology ; Cell Line, Tumor ; Female ; Lymphocyte Activation/immunology ; Lymphocytes/immunology ; Mice ; Mice, Inbred C57BL ; Receptor, Interferon alpha-beta/immunology ; Signal Transduction/immunology
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Grant Information:: 1127757 Cancer Council Victoria
Contributed Indexing:: Keywords: Antitumor immunity; Breast cancer; Immunotherapy; Natural killer cells; Type I interferon
Substance Nomenclature:: 0 (Interferon Type I)
156986-95-7 (Receptor, Interferon alpha-beta)
Entry Date(s):: Date Created: 20210115 Date Completed: 20210726 Latest Revision: 20210726
Update Code:: 20240105
DOI:: 10.1007/s00262-021-02857-z
PMID:: 33449132
: Czasopismo naukowe

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Competent type I IFN signaling is the lynchpin of most immune surveillance mechanisms and has recently proven critical to the efficacy of several anticancer agents. Expression of the type I IFN receptor, IFNAR, underpins type I IFN responsiveness in all cells and facilitates the activation and cytotoxic potential of lymphocytes, while loss of IFNAR on lymphocytes has previously been associated with tumor progression and poor patient survival. This study underscores the importance of intact type I IFN signaling to NK cells in the regulation of tumorigenesis and metastasis, whereby ablation of NK cell IFNAR1 impairs antitumor activity and tumor clearance. Using a preclinical model of triple negative breast cancer, we identified that intact IFNAR on NK cells is required for an effective response to type I IFN-inducing immunotherapeutics that may be mediated by pathways associated with NK cell degranulation. Taken together, these data provide a rationale for considering the IFNAR status on NK cells when devising therapeutic strategies aimed at inducing systemic type I IFN signaling in breast cancer.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

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