Type 2 bias of T cells expanded from the blood of melanoma patients switched to type 1 by IL-12p70 mRNA-transfected dendritic cells

Kira Minkis, Daniel G. Kavanagh, Galit Alter, Dusan Bogunovic, David O'Neill, Sylvia Adams, Anna Pavlick, Bruce D. Walker, Mark A. Brockman, Rajesh T. Gandhi, Nina Bhardwaj

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Melanoma patients may exhibit a TH2-skewed cytokine profile within blood and tumor-infiltrating lymphocytes. Therapies that induce beneficial TH1-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 β, 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 TH1 responses. In this study, human DC were transfected with IL-12p70 mRNA and tested for their ability to alter the TH2 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 TH1 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.

Original languageEnglish
Pages (from-to)9441-9450
Number of pages10
JournalCancer Research
Volume68
Issue number22
DOIs
StatePublished - 15 Nov 2008
Externally publishedYes

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