Sustained type I interferon reinforces NK cell–mediated cancer immunosurveillance during chronic virus infection

Ji Hoon Oh, Myeong Joon Kim, Seong Jin Choi, Young Ho Ban, Heung Kyu Lee, Eui Cheol Shin, Kyung Mi Lee, Sang Jun Ha

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

The importance of natural killer (NK) cells in the early immune response to viral or bacterial infection is well known. However, the phenotype, function, and physiologic role of NK cells during the late stage of persistent viral infection have not been extensively studied. Here, we characterized NK cells in mice persistently infected with lymphocytic choriomeningitis virus clone 13 and showed that in contrast to NK cells from acutely infected or uninfected mice, NK cells from chronically infected mice expressed a terminally differentiated phenotype, stronger cytotoxicity, and reduced inhibitory receptor expression. In an in vivo tumor model, chronically infected mice exhibited significantly delayed tumor progression in an NK cell–dependent manner. NK cells from chronically infected mice also expressed high STAT1, and blocking the type I interferon (IFN) receptor revealed that type I IFN signaling directly regulated NK cell cytotoxicity. Our findings indicate that sustained type I IFN signaling during chronic viral infection potentiates the cytolytic function of NK cells and contributes to NK cell–dependent host immune surveillance.

Original languageEnglish
Pages (from-to)584-599
Number of pages16
JournalCancer Immunology Research
Volume7
Issue number4
DOIs
Publication statusPublished - 2019 Apr

Bibliographical note

Funding Information:
This study was supported by the Basic Science Research Program (2018R1A2A1A05076997 and 2017R1A5A1014560 to S-.J. Ha and 2017R1A2B3004828 to K-.M. Lee) and the Bio & Medical Technology Development Program (2018M3A9H3024850 to S-.J. Ha) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning.

Publisher Copyright:
©2019 American Association for Cancer Research.

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cancer Research

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