Human γδ T lymphocytes induce robust NK cell-mediated antitumor cytotoxicity through CD137 engagement

Amudhan Maniar, Xiaoyu Zhang, Wei Lin, Brian R. Gastman, C. David Pauza, Scott E. Strome, Andrei I. Chapoval

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

Natural killer (NK) cells are innate effector lymphocytes that control the growth of major histocompatibility complex class I negative tumors. We show here that γδ T lymphocytes, expanded in vitro in the presence isopentenylpyrophosphate (IPP), induce NK cell-mediated killing of tumors that are usually resistant to NK cytolysis. The induction of cytotoxicity toward these resistant tumors requires priming of NK cells by immobilized human immunoglobulin G1 and costimulation through CD137L expressed on activated γδ T lymphocytes. This costimulation increases NKG2D expression on the NK-cell surface, which is directly responsible for tumor cell lysis. Moreover, culturing peripheral blood mononuclear cells with zoledronic acid, a γδ T lymphocyte activating agent, enhances NK-cell direct cytotoxicity and antibody-dependent cellular cytotoxicity against hematopoietic and nonhematopoietic tumors. Our data reveal a novel function of human γδ T lymphocytes in the regulation of NK cell-mediated cytotoxicity and provide rationale for the use of strategies to manipulate the CD137 pathway to augment innate antitumor immunity.

Original languageEnglish (US)
Pages (from-to)1726-1733
Number of pages8
JournalBlood
Volume116
Issue number10
DOIs
StatePublished - Sep 9 2010

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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