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Journal of Investigative Medicine:
doi: 10.231/JIM.0000000000000031
Original Articles

Tobacco Smoke–Induced Immunologic Changes May Contribute to Oral Carcinogenesis

Schierl, Michael MD*†; Patel, Daxesh MD†‡; Ding, Wanhong MD*; Kochhar, Amit MD†§; Adhami, Katayun MD*; Zhou, Xi Kathy PhD; Dannenberg, Andrew J. MD; Granstein, Richard D. MD*

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Abstract

Objective

The objective of this study was to determine if tobacco smoke (TS), a risk factor for cancers of the aerodigestive tract, may contribute to oral carcinogenesis, in part, by suppressing local immunity.

Methods

Mice were placed in Plexiglas holders in which they breathed TS through the nose and mouth for 1 hour daily for 21 days. Control mice breathed room air in the same manner. One day after the last exposure, mice were immunized by application of oxazolone to each buccal mucosa. Control mice were mock immunized by application of vehicle alone. Five days later, all mice were challenged on the ears with oxazolone, and 24-hour ear swelling assessed as contact hypersensitivity.

Results

Mice exposed to TS had a significantly smaller contact hypersensitivity response compared with controls. When subsequently reimmunized on the glabrous skin, mice originally primed through TS-exposed mucosa could not be fully immunized, indicating induction of immunologic tolerance by exposure to hapten through TS-perturbed mucosa. Immunocompetent mice exposed to TS in this manner and challenged by submucosal placement of a syngeneic malignant tumor had significantly increased tumor growth over time compared with controls. No difference in growth rate was observed when the experiment was performed with natural killer cell–deficient, SCID (severe combined immunodeficiency) mice. In addition, exposure of epidermal Langerhans cells in vitro to an aqueous extract of TS impaired their ability to undergo maturation and to present antigen to responsive T cells.

Conclusions

Immunologic changes induced in the oral cavity by exposure to TS may play a role in the development of oral cancers.

Copyright © 2014 by The American Federation for Medical Research

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