Activation of NFkB In Oral Tumor By Monocytes-Macrophages

Objective: We have previously shown that increased induction of NFκB in oral tumors is an important resistant factor for Natural Killer (NK) cell mediated cytotoxicity. Therefore, the objective of this study is to identify and characterize the subsets of immune effectors which contribute to increased induction of NFκB in oral tumors during their interaction.

Methods: UCLA-1 and UCLA-2 primary oral tumors, vector-alone and IκB (S32AS36A) super-repressor transfected HEp2 cells, and 293T cells were transfected with NFκB luciferase reporter vector before they were co-cultured in the presence and absence of purified Monocytes, Natural Killer cells, Polymorphonuclear cells and unfractionated Peripheral blood lymphocytes (PBLs) as well as Peripheral Blood Mononuclear Cells (PBMCs). The levels of NFκB activation was determined and related to the levels of cell survival or death of oral tumors in the co-cultures of immune effectors with the oral tumors.

Results: untreated NK cells were unable to kill or increase NFκB in oral tumor cells. IL-2 activated NK cells decreased the levels of NFκB in oral tumors likely due to their potent death inducing capacity in oral tumors. On the other hand monocytes were potent inducers of NFκB in oral tumors and they did not have the ability to lyse oral tumors. PMNs neither lysed nor induced NFκB in oral tumors. On the basis of NFκB induction, two subpopulations of monocytes were identified, and their ability to contribute to oral tumor growth and resistance were characterized.

Conclusion: Monocytes but not NK cells or PMNs contribute significantly to oral tumor resistance by increasing NFκB levels. The minor subpopulation of CD14+CD16+ monocytes, contribute the most, and therefore, they may be the primary population which support the growth, expansion and resistance of oral tumors.