Type I IFN contributes to NK cell homeostasis, activation, and antitumor function

Jeremy B. Swann, Yoshihiro Hayakawa, Nadeen Zerafa, Kathleen C.F. Sheehan, Bernadette Scott, Robert D. Schreiber, Paul Hertzog, Mark J. Smyth

Research output: Contribution to journalArticlepeer-review

179 Scopus citations

Abstract

This study demonstrates that type I IFNs are an early and critical regulator of NK cell numbers, activation, and antitumor activity. Using both IFNAR1- and IFNAR2-deficient mice, as well as an IFNAR1-blocking Ab, we demonstrate that endogenous type I IFN is critical for controlling NK cell-mediated antitumor responses in many experimental tumor models, including protection from methylcholanthrene-induced sarcomas, resistance to the NK cell-sensitive RMA-S tumor and cytokine immunotherapy of lung metastases. Protection from RMA-S afforded by endogenous type I IFN is more potent than that of other effector molecules such as IFN-γ, IL-12, IL-18, and perforin. Furthermore, cytokine immunotherapy using IL-12, IL-18, or IL-21 was effective in the absence of endogenous type I IFN, however the antimetastatic activity of IL-2 was abrogated in IFNAR-deficient mice, primarily due to a defect in IL-2-induced cytotoxic activity. This study demonstrates that endogenous type I IFN is a central mediator of NK cell antitumor responses.

Original languageEnglish
Pages (from-to)7540-7549
Number of pages10
JournalJournal of Immunology
Volume178
Issue number12
DOIs
StatePublished - Jun 15 2007

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