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

JB Swann, Y Hayakawa, N Zerafa… - The Journal of …, 2007 - journals.aai.org
JB Swann, Y Hayakawa, N Zerafa, KCF Sheehan, B Scott, RD Schreiber, P Hertzog
The Journal of Immunology, 2007journals.aai.org
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 …
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.
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