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Tobacco Smoke–Induced Immunologic Changes May Contribute to Oral Carcinogenesis
  1. Michael Schierl, MD*†,
  2. Daxesh Patel, MD†‡,
  3. Wanhong Ding, MD*,
  4. Amit Kochhar, MD†§,
  5. Katayun Adhami, MD*,
  6. Xi Kathy Zhou, PhD,
  7. Andrew J. Dannenberg, MD,
  8. Richard D. Granstein, MD*
  1. From the Departments of *Dermatology and †Medicine, Weill Cornell Medical College, New York, NY ‡Department of Surgery (Head and Neck Service), Memorial Sloan-Kettering Cancer Center, New York, NY; §Department of Otolaryngology–Head and Neck Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD; and ∥Department of Public Health, Weill Cornell Medical College, New York, NY.
  1. Received September 2, 2013, and in revised form October 21, 2013.
  2. Accepted for publication October 22, 2013.
  3. Reprints: Richard D. Granstein, MD, Department of Dermatology, Weill Cornell Medical College, 1305 York Ave, 9th Floor, New York, NY 10021. E-mail: rdgranst{at}
  4. Drs. Schierl and Patel contributed equally to this work.
  5. This study was supported by NIDCD T32 DC 000027 (to A.K.) and NIH UL1-RR024996 (to X.K.Z.) and by a gift from the Jacob L. and Lillian Holtzmann Foundation (to R.D.G.), contributions from the Carl and Fay Simons Family Trust (to R.D.G.) and the Seth Sprague Educational and Charitable Foundation (to R.D.G.), and grants from the Flight Attendants Medical Research Institute (to A.J.D.), the Edith C. Blum Foundation (R.D.G.), and the Lewis B. and Dorothy Cullman Foundation (to R.D.G.).


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.

Key Words
  • tobacco
  • mucosa
  • cancer
  • immune suppression
  • mouse

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