This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Minkis, K. Articles by Bhardwaj, N. Search for Related Content PubMed PubMed Citation Articles by Minkis, K. Articles by Bhardwaj, N.

Type 2 Bias of T Cells Expanded from the Blood of Melanoma Patients Switched to Type 1 by IL-12p70 mRNA–Transfected Dendritic Cells

¹ New York University School of Medicine, New York, New York; ² Howard Hughes Medical Institute; and ³ Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Requests for reprints: Nina Bhardwaj, New York University Medical Center, 550 First Avenue, New York, NY 10016. Phone: 212-263-5814; Fax: 212-263-6729; E-mail: Nina.Bhardwaj{at}nyumc.org.

Key Words: Dendritic Cells • Melanoma • Vaccines • IL-12 • immunotherapy

Melanoma patients may exhibit a T_H2-skewed cytokine profile within blood and tumor-infiltrating lymphocytes. Therapies that induce beneficial T_H1-type tumor-specific immune responses, therefore, are highly desirable. Dendritic cells (DC) are widely used as immune adjuvants for cancer. Before their administration, DC are generally induced to mature with a cocktail of recombinant cytokines [interleukin (IL)-1β, tumor necrosis factor , and IL-6] and prostaglandin E₂ (PGE₂), which is added to preserve the ability of DC to migrate to draining lymph nodes. However, PGE₂ suppresses the production of IL-12p70, a cytokine essential for differentiation of T_H1 responses. In this study, human DC were transfected with IL-12p70 mRNA and tested for their ability to alter the T_H2 type bias manifested by blood T cells of patients with melanoma. Transfected DC secreted high levels of bioactive IL-12p70, as indicated by their capacity to enhance natural killer cell activity, skew T_H1 responses in allogeneic mixed lymphocyte reactions through reduction of IL-4 and IL-5, and prime CD8⁺ T cells to the melanoma-associated antigen Melan A/MART-1. Furthermore, T-cell lines primed in vitro from the blood of melanoma patients showed strong type 2 skewing that was dramatically reversed by IL-12p70 transfection of autologous DC. Thus, IL-12p70 transfection of clinical DC preparations may enhance type 1 antitumor responses and may thereby contribute to effective immune-based therapy. [Cancer Res 2008;68(22):9441–50]