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      Use of Carcinogen-induced Premalignant Oral Lesions in a Dendritic Cell-based Vaccine to Stimulate Immune Reactivity Against Both Premalignant Oral Lesions and Oral Cancer

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          Summary

          Select groups of premalignant oral lesions carry a high risk of development of secondary premalignant lesions and oral squamous cell carcinoma (OSCC). The goal of the present study was to determine the feasibility of using premalignant lesion-pulsed dendritic cells as a treatment option to prevent development of secondary lesions and development of OSCC. Mice that were treated with the carcinogen 4-nitroquinoline-1-oxide (4NQO) developed premalignant oral lesions and, subsequently, OSCC. Immunohistochemical analyses showed that these 4NQO-induced lesions and OSCC both overexpressed the tumor antigens epidermal growth factor receptor, RAGE and, to a lesser extent, MUC1. Because there was shared overexpression of tumor antigens on premalignant oral lesions and OSCC, dendritic cells pulsed with lysates of 4NQO-induced premalignant lesion cells were tested in vitro and in vivo for their capacity to stimulate T-cell reactivity to premalignant lesion cells and to OSCC. Spleen cells that were sensitized during coculture or in vivo with premalignant lesion-pulsed dendritic cells were cytolytic toward both premalignant lesion cells and OSCC, and secreted increased levels of interferon-γ in response to challenge with premalignant lesion cells or OSCC as compared with spleen cells that were sensitized with keratinocyte-pulsed dendritic cells. Levels of CD8 + Tcells and interferon-γ release were also increased in lesions of mice that were vaccinated with premalignant lesion-pulsed dendritic cells. The mice that were vaccinated against premalignant lesions were also more resistant to OSCC challenge. These studies show the feasibility of using premalignant oral lesions to stimulate immune reactivity against both premalignant oral lesions and OSCC.

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          Author and article information

          Journal
          9706083
          21058
          J Immunother
          J. Immunother.
          Journal of immunotherapy (Hagerstown, Md. : 1997)
          1524-9557
          1537-4513
          19 April 2018
          Feb-Mar 2008
          30 April 2018
          : 31
          : 2
          : 148-156
          Affiliations
          [* ]Research Service, Ralph H. Johnson VA Medical Center, Medical University of South Carolina, Charleston, South Carolina
          []Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina
          []Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
          Author notes
          Reprints: M. Rita I. Young, Research Service (151), 109 Bee Street, Ralph H. Johnson Veterans Affairs Hospital, Charleston, SC 29401-5799 ( rita.young@ 123456med.va.gov )
          Article
          PMC5925417 PMC5925417 5925417 nihpa960685
          10.1097/CJI.0b013e31815bdbf5
          5925417
          18481384
          b39f9894-8e50-4f61-8021-5a5758c2c4d6
          History
          Categories
          Article

          OSCC,vaccine,premalignant,oral lesions,oral cancer
          OSCC, vaccine, premalignant, oral lesions, oral cancer

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