TY - JOUR
T1 - Potent induction of TNF-α during interaction of immune effectors with oral tumors as a potential mechanism for the loss of NK cell viability and function
AU - Romero-Reyes, Marcela
AU - Head, Christian
AU - Cacalano, Nicholas A.
AU - Jewett, Anahid
N1 - Funding Information:
Acknowledgement This work was supported by RO1-12880 from NIH-NIDCR. We acknowledge the excellent technical assistance of Niloufar Nouri Mahdavie, Sam Moghtader, Jing Lee and Mita Jetwani. We thank Dr. Chris W. Kaplan for preparing the cultures of F. nucleatum.
PY - 2007/11
Y1 - 2007/11
N2 - The inhibitory role of TNF-α on survival of naïve and IL-2 treated NK cells has been demonstrated in the past. However, its effect on the function of these cells against tumor cells, in particular against oral tumors has not been established. We investigated the significance of secreted TNF-α in death and functional loss of splenocytes and NK cells in ex-vivo cultures with oral tumors. Oral tumors trigger potent secretion of TNF-α by human and murine immune effectors. Absence of TNF-α increases the cytotoxic activity and secretion of IFN-γ by IL-2 treated splenocytes and NK cells in co-cultures with MOK L2D1+/p53-/- oral tumor cells. IL-2 treated splenocytes and NK cells from TNF-α -/- mice survive and proliferate more when compared to cells from TNF-α +/+ mice. Cell death induced by F. nucleatum, an oral bacteria, in TNF-α -/- splenocytes are considerably lower than that induced in TNF-α +/+ splenocytes where potent release of TNF-α is reproducibly observed. Addition of exogenous rTNF-α to IL-2 treated splenocytes and NK cells decreased survival and function of splenocytes and NK cells obtained from TNF-α -/- mice against oral tumors. These findings suggest that potent induction of TNF-α during interaction of immune effectors with oral tumors and/or oral bacteria is an important factor in decreasing the function and survival of cytotoxic immune effectors. Strategies to neutralize TNF-α may be beneficial in the treatment of oral cancers.
AB - The inhibitory role of TNF-α on survival of naïve and IL-2 treated NK cells has been demonstrated in the past. However, its effect on the function of these cells against tumor cells, in particular against oral tumors has not been established. We investigated the significance of secreted TNF-α in death and functional loss of splenocytes and NK cells in ex-vivo cultures with oral tumors. Oral tumors trigger potent secretion of TNF-α by human and murine immune effectors. Absence of TNF-α increases the cytotoxic activity and secretion of IFN-γ by IL-2 treated splenocytes and NK cells in co-cultures with MOK L2D1+/p53-/- oral tumor cells. IL-2 treated splenocytes and NK cells from TNF-α -/- mice survive and proliferate more when compared to cells from TNF-α +/+ mice. Cell death induced by F. nucleatum, an oral bacteria, in TNF-α -/- splenocytes are considerably lower than that induced in TNF-α +/+ splenocytes where potent release of TNF-α is reproducibly observed. Addition of exogenous rTNF-α to IL-2 treated splenocytes and NK cells decreased survival and function of splenocytes and NK cells obtained from TNF-α -/- mice against oral tumors. These findings suggest that potent induction of TNF-α during interaction of immune effectors with oral tumors and/or oral bacteria is an important factor in decreasing the function and survival of cytotoxic immune effectors. Strategies to neutralize TNF-α may be beneficial in the treatment of oral cancers.
KW - Apoptosis
KW - IFN-γ
KW - Natural killer cells
KW - TNF-α
KW - TNF-α -/-
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U2 - 10.1007/s10495-007-0112-6
DO - 10.1007/s10495-007-0112-6
M3 - Article
C2 - 17713857
AN - SCOPUS:34848871935
SN - 1360-8185
VL - 12
SP - 2063
EP - 2075
JO - Apoptosis
JF - Apoptosis
IS - 11
ER -