Inhibition of nuclear factor kappa B (NFκB) activity in oral tumor cells prevents depletion of NK cells and increases their functional activation

Anahid Jewett, Nicholas A. Cacalano, Antonia Teruel, Marcela Romero, Marjan Rashedi, Meiying Wang, Hiromi Nakamura

Research output: Contribution to journalArticlepeer-review


The aim of this study is to identify candidate factors which may be responsible for the functional inactivation and depletion of NK cells by tumor cells. Inhibition of NFκB activity by an IκB super-repressor in HEp2 cells, a cell line commonly used as an oral tumor model, blocked tumor-induced NK cell death, and increased the function of NK cells significantly. Increased expression of CD69 early activation antigen on NK cells as well as augmented proliferation and secretion of IFN-γ by NK cells were observed when these cells were co-incubated with IκB super-repressor transfected HEp2 cells (HEp2-IκB(S32AS36A)). More importantly, the secretion of IL-6 was significantly inhibited when NK cells were co-cultured with HEp2-IκB(S32AS36A) cells. In addition, the survival and function of cytotoxic effector cells remained significantly elevated in the presence of IFN-γ-treated HEp2-IκB(S32AS36A) cells when compared to either untreated or IFN-γ-treated vector-alone transfected HEp2 cells. Similar findings to those obtained using purified peripheral blood NK cells were also observed when non-fractionated peripheral blood mononuclear cells were used in the co-cultures of immune effectors with HEp2 cell transfectants. Addition of recombinant human IL-6 to the co-cultures of immune effectors with the NFκB knockdown HEp2 tumor cells substantially decreased the levels of secreted IFN-γ. Thus, the results presented in this paper suggest that the inhibition of NFκB function in oral tumors may serve to activate and expand the function and numbers of NK cells. Moreover, NFκB-mediated increase in IL-6 secretion by oral tumors may in part be responsible for the observed inactivation and death of the immune effectors.

Original languageEnglish (US)
Pages (from-to)1052-1063
Number of pages12
JournalCancer Immunology, Immunotherapy
Issue number9
StatePublished - Sep 2006


  • Apoptosis
  • IFN-γ
  • IL-6
  • NFκB
  • NK
  • Natural killer
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research


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