Head and neck cancer: meeting summary and research opportunities.

Department of Otolaryngology and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Cancer Research (Impact Factor: 8.65). 12/2004; 64(21):8126-9. DOI: 10.1158/0008-5472.CAN-04-2445
Source: PubMed

ABSTRACT Head and neck squamous cell carcinoma (HNSCC) is the most common malignant neoplasm arising in the mucosa of the upper aerodigestive tract. Nearly two thirds of patients present with advanced (stage III and IV) disease. Fifty percent of HNSCC patients die of their disease, and 5% of HNSCC patients per year will develop additional second primary tumors. Currently used therapeutic modalities (surgery, radiation, and/or chemotherapy) have been associated with rather modest improvements in patient survival. The Head and Neck Cancer: Research and Therapeutic Opportunities Workshop (held in Washington, DC, May 24-26, 2004) was organized by the Division of Cancer Biology at the National Cancer Institute to identify research areas and directions that will advance understanding of HNSCC biology and accelerate clinical translation. The primary goal of the workshop was to identify the barriers that impede basic science discovery and the translation of these developments to the clinical setting. Over a 2.5-day period, experts in both HNSCC and other cancer-related fields met to identify and prioritize the key areas for future research. The overall consensus was that HNSCC is a relatively understudied malignancy and that investigations that focus on the biology of this tumor have the potential to impact significantly on the prevention and treatment of epithelial malignancies. The chief objective is to communicate these research goals to the cancer biology community and encourage more interest in HNSCC as a tumor model to test translational research hypotheses.

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    ABSTRACT: Introduction: Several literature sources have suggested that subjects with head and neck squamous cell carcinoma (HNSCC) display significant abnormalities of immunocompetent cells and cytokine secretion. Serious side effects and only a limited success with traditional therapies in HNSCC dictate the need for newer therapies. Areas covered: This article comprehensively reviews the immune system alterations in HNSCC and the rationale behind various experimental immunotherapies, aiming at keeping this disease under control. Relevant publications were identified through the PubMed database search. The ongoing clinical trials regarding experimental immunotherapy agents in HNSCC were accessed at . The obtained information was thoroughly analyzed and systematized. Expert opinion: Important and severe immune defects including T-cell dysfunction, cytokine alterations and antigen presentation defects are present in patients with HNSCC. In addition, tumor microenvironment was shown to play a critical role in the HNSCC progression. These discoveries have triggered a growing interest in immunotherapy as a potential treatment strategy for HNSCC. Effective immunotherapy could avoid the toxic side effects plaguing the current management of HNSCC. It is also hoped that immunotherapy will have long-lasting effects due to induction of immunologic memory. Promising directions include nonspecific immune stimulation, targeting specific HNSCC tumor antigens and therapeutic vaccines among others. These new agents may expand the existing therapy options for HNSCC in future.
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is marked by immunosuppression, a state in which the established tumor escapes immune attack. However, the impact of the premalignant and tumor microenvironments on immune reactivity has yet to be elucidated. The purpose of this study was to determine how soluble mediators from cells established from carcinogen-induced oral premalignant lesions and HNSCC modulate immune cell cytokine production. It was found that premalignant cells secrete significantly increased levels of G-CSF, RANTES, MCP-1, and PGE2 compared to HNSCC cells. Splenocytes incubated with premalignant supernatant secreted significantly increased levels of Th1-, Th2-, and Th17-associated cytokines compared to splenocytes incubated with HNSCC supernatant. These studies demonstrate that whereas the premalignant microenvironment elicits proinflammatory cytokine production, the tumor microenvironment is significantly less immune stimulatory and may contribute to immunosuppression in established HNSCC.
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