title: Interactions of dendritic cells with cancer cells and modulation of surface molecules affect functional properties of CD8+ T cells.
abstract: To understand the interaction of dendritic cells (DCs) with cancer cells, we investigated molecular changes in DCs following co-culture with cancer cells. DCs co-cultured with Jurkat cancer cells showed remarkable down-regulation of MHC class I molecules, while DCs co-cultured with MCF-7 cancer cells showed minimal changes. Interestingly, down-regulation of MHC class I on DCs was not observed upon treatment with Jurkat cell lysate or culture supernatant, suggesting the importance of direct cell-cell interactions. The expressions of CD40, CD80, CD83, MHC class II, and IL-12p40 on DCs co-cultured with Jurkat cells were only slightly affected. In contrast, DCs co-cultured with MCF-7 cells showed increased expressions of CD80, CD83, CD86, and IL-12p40. Furthermore, DCs co-cultured with Jurkat cells showed a down-regulation of low molecular weight polypeptides (LMP) 7, and of transporter associated with antigen processing (TAP) 1 and 2 at the mRNA expression level. LMP7, TAP2 and β2-microglobulin (β2M) were also down-regulated at the protein level. We further demonstrated how altered expression of MHC class I on DCs caused by co-culture with cancer cells affected autologous CD8(+) T cells, using the model MHC class I-presented HSV antigen. We found that DCs that had been HSV-treated and co-cultured with Jurkat cells showed a reduced potency to activate CD8(+) T cells. In contrast, HSV-treated DCs that had been co-cultured with MCF-7 cells induced activation of CD8(+) T cells, including high expression of CD25, CD69, granzyme B and cytokines, TNF-α and IFN-γ.
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Seo
authors.forename: Gi Rak
authors.initials: GR
authors.lastname: Kim
authors.forename: Young Min
authors.initials: YM
authors.lastname: Son
authors.forename: Deok-Chun
authors.initials: DC
authors.lastname: Yang
authors.forename: Hyuk
authors.initials: H
authors.lastname: Chu
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Min
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D015395:Histocompatibility Antigens Class I