A role of interferon-γ (IFN-γ) in tumor immunity: T cells with the capacity to reject tumor cells are generated but fail to migrate to tumor sites in IFN-γ-deficient mice

Chigusa Nakajima, Yasuhiro Uekusa, Masayuki Iwasaki, Nobuya Yamaguchi, Takao Mukai, Ping Gao, Michio Tomura, Shiro Ono, Takahiro Tsujimura, Hiromi Fujiwara, Toshiyuki Hamaoka

Research output: Contribution to journalArticlepeer-review

Abstract

IFN-γ-deficient (IFN-γ-/-) mice induce potent in vitro immune responses such as anti-allo mixed lymphocyte reaction and CTL responses, whereas they often fail to exhibit in vivo immunity. Here, we investigated whether there exists a defect in tumor rejection responses and if so, which process of responses is impaired. IFN-γ-/- and wild-type (WT) BALB/c mice were immunized with attenuated syngeneic CSA1M tumor cells. The capacity of T cells to mediate tumor protection was examined in Winn assays to assess the growth of tumor cells admixed with tumor-sensitized T cells. Splenic T cells from both groups of mice exhibited comparable levels of tumor-neutralizing activity. When portions of immunized mice were directly challenged with viable tumor cells, tumor rejection was induced only in WT mice. CD4+ and CD8+ T-cell infiltration were observed at the site of tumor challenge in WT mice, whereas such a T-cell infiltration did not occur in IFN-γ-/- mice. Similarly, splenic T cells from interleukin 12-treated CSA1M-bearing IFN-γ-/- and WT mice neutralized tumor cells at comparable efficacies in Winn assays. However, the migration of these T cells to tumor masses and the resultant interleukin 12-induced tumor regression took place in WT mice, but neither intratumoral T-cell infiltration nor tumor regression occurred in IFN-γ-/- mice. These results indicate a critical requirement for IFN-γ in the process of inducing T-cell migration to tumor sites rather than of generating antitumor protective T cells.

Original languageEnglish (US)
Pages (from-to)3399-3405
Number of pages7
JournalCancer Research
Volume61
Issue number8
StatePublished - Apr 15 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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