Memory type 2 helper T cells induce long-lasting antitumor immunity by activating natural killer cells

Masayuki Kitajima, Toshihiro Ito, Damon J. Tumes, Yusuke Endo, Atsushi Onodera, Kahoko Hashimoto, Shinichiro Motohashi, Masakatsu Yamashita, Takashi Nishimura, Steven F. Ziegler, Toshinori Nakayama

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22 Citations (Scopus)


Functionally polarized helper T cells (Th cells) play crucial roles in the induction of tumor immunity. There is considerable knowledge about the contributions of IFN-producing Th1 cells that supports the role of cytotoxic cluster of differentiation (CD8) T cells and natural killer (NK) cells, but much less is known about how IL-4-producing Th2 cells contribute to tumor immunity. In this study, we investigated the cellular and molecular mechanisms employed by memory Th2 cells in sustaining tumor immunity by using a mouse model system wherein ovalbumin (OVA) is used as a specific tumor antigen. In this model, we found that OVA-specific memory Th2 cells exerted potent and long-lasting antitumor effects against NK-sensitive OVA-expressing tumor cells, wherein antitumor effects were mediated by NK cells. Specifically, NK cell cytotoxic activity and expression of perforin and granzyme B were dramatically enhanced by the activation of memory Th2 cells. Interleukin 4 (IL-4) produced by memory Th2 cells in vivo was critical for the antitumor effects of the NK cells, which IL-4 directly stimulated to induce their perforin- and granzyme-B-dependent cytotoxic activity. Our findings show that memory Th2 cells can induce potent antitumor immunity through IL-4-induced activation of NK cells, suggesting potential applications in cellular therapy for cancer patients.

Original languageEnglish
Pages (from-to)4790-4798
Number of pages9
JournalCancer Research
Issue number14
Publication statusPublished or Issued - 15 Jul 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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