CD1d-restricted natural killer T cells can down-regulate tumor immunosurveillance independent of interleukin-4 receptor-signal transducer and activator of transcription 6 or transforming growth factor-β

Masaki Terabe, Chand Khanna, Seuli Bose, Fraia Melchionda, Arnulfo Mendoza, Crystal L. Mackall, Lee J. Helman, Jay A. Berzofsky

Research output: Contribution to journalArticlepeer-review

Abstract

It has been shown previously that the suppression of tumor immunosurveillance may be a mechanism by which tumors resist immune detection and elimination. In this study, we evaluated the role of the immunoregulatory natural killer T (NKT) cells in the biology of immunosurveillance of osteosarcoina. The K7M2 mouse osteosarcoma cell line was implanted orthotopically into wild-type and NKT cell-deficient CD1d knockout (KO) BALB/c mice, and mice were monitored for growth of primary tumors. Further, we examined the role of CD4+ and/or CD8+ cells by depleting the cells in vivo and measuring CTL activity in vitro. We also asked the role of interleukin (IL)-4 receptor α(IL-4Rα)-signal transducer and activator of transcription 6 (STAT6) signaling, including IL-13, and transforming growth factor β(TGF-β) by using gene-disrupted mice or treating mice with cytokine antagonists. We were surprised to find a high rate of rejection of osteosarcoma primary tumors in 88% (14 of 16) of CD1d KO mice compared with syngeneic wild-type BALB/c mice that showed rejection of tumor in <24% of mice. Further studies suggested that the rejection of tumor in CD1d KO mice was dependent on CD8+ lymphocytes. Distinct from other m urine tumor models, the negative regulation induced by CD1d-restricted NKT cells was not dependent on IL-4Rα-STAT6 signaling, including IL-13, or on TGF-β. These data suggest that a novel CD1d-restricted NKT cell-mediated mechanism for tumor immunosuppression is active in the K7M2 osteosarcoma model and that NKT cells can regulate immunosurveillance through more than one pathway.

Original languageEnglish (US)
Pages (from-to)3869-3875
Number of pages7
JournalCancer Research
Volume66
Issue number7
DOIs
StatePublished - Apr 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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