title: Molecular profiling of tumor-specific TH1 cells activated in vivo.
abstract: The central role of tumor-specific TH1 cells in anticancer immune responses is becoming increasingly appreciated. However, little is known about how these cells are generated in vivo. Here, we used flow cytometry and gene expression microarrays to characterize the primary activation and TH1 differentiation of naïve tumor-specific CD4+T cells in a mouse model of cancer immunosurveillance. We took advantage of T-cell receptor-transgenic mice in which CD4+T cells recognize a tumor-specific antigen secreted by MHC class II-negative MOPC315 myeloma cells. Cancer cells were injected subcutaneously and T-cell activation was analyzed in draining lymph nodes and at the incipient tumor site 8 d later. Upon activation and migration to incipient tumor sites, tumor-specific CD4+T cells exhibited the upregulation of 29 cell-surface molecules (CD2, CD5, CD11a, CD18, CD25, CD28, CD44, CD45, CD49d, CD51, CD54, CD69, CD71, CD83, CD86, CD90, CD95, CD102, CD122, CD153, CD166, CD200, CD249, CD254, CD274, CD279, Ly6C, MHC class I and CCR7) and the downregulation of five (CD27, CD31, CD45RB, CD62L and CD126). Activated CD4+T cells produced interferon γ, a cytokine consistent with a TH1-polarized response, tumor necrosis factor α as well as interleukin (IL)-2, IL-3 and IL-10. The activation of naïve tumor-specific CD4+T cells in draining lymph nodes resulted in the upregulation of 609 genes and the downregulation of 284 genes. The bioinformatic analysis of differentially expressed genes identified functional pathways related to tumor-specific TH1 cell activation. This study may represent a useful resource to guide the development of TH1-based immunotherapies against cancer.
authors.affiliation: Centre for Immune Regulation; Department of Immunology; Oslo University Hospital Rikshospitalet and University of Oslo; Oslo, Norway.
authors.forename: Kristina Berg
authors.initials: KB
authors.lastname: Lorvik
authors.forename: Ole Audun Werner
authors.initials: OA
authors.lastname: Haabeth
authors.forename: Trevor
authors.initials: T
authors.lastname: Clancy
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.forename: Alexandre
authors.initials: A
authors.lastname: Corthay
keywords: TH1; cancer immunosurveillance; flow cytometry; gene expression microarray; tumor-specific CD4+ T cells