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Journal of Dental Research
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*Oral Cancer
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CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE

Emerging Mechanisms of Immunosuppression in Oral Cancers

A. Jewett1,*, C. Head2 and N.A. Cacalano3

1 The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, and Division of Oral Biology and Medicine, Jonsson Comprehensive Cancer Center (JCCC),
2 Department of Head and Neck surgery, and
3 Department of Radiation Oncology, UCLA School of Dentistry and Medicine, 10833 Le Conte Ave., University of California, Los Angeles, CA 90095-1668, USA

Correspondence: * corresponding author, ajewett{at}ucla.edu

Mounting effective anti-tumor immune responses against tumors by both the innate and adaptive immune effectors is important for the clearance of tumors. However, accumulated evidence indicates that immune responses that should otherwise suppress or eliminate transformed cells are themselves suppressed by the function of tumor cells in a variety of cancer patients, including those with oral cancers. Signaling abnormalities, spontaneous apoptosis, and reduced proliferation and function of circulating natural killer cells (NK), T-cells, dendritic cells (DC), and tumor-infiltrating lymphocytes (TILs) have been documented previously in oral cancer patients. Several mechanisms have been proposed for the functional deficiencies of tumor-associated immune cells in oral cancer patients. Both soluble factors and contact-mediated immunosuppression by the tumor cells have been implicated in the inhibition of immune cell function and the progression of tumors. More recently, elevated levels and function of key transcription factors in tumor cells, particularly NF{kappa}B and STAT3, have been shown to mediate immune suppression in the tumor microenvironment. This review will focus on these emerging mechanisms of immunosuppression in oral cancers.

Key Words: apoptosis • NF{kappa}B • TNF-{alpha} • IFN-{gamma} • NK • IL-6 • MCP-1 • RANTES • oral cancer • immune suppression

Journal of Dental Research, Vol. 85, No. 12, 1061-1073 (2006)
DOI: 10.1177/154405910608501201
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