PMID- 10969791 OWN - NLM STAT- MEDLINE DCOM- 20000914 LR - 20181130 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 60 IP - 16 DP - 2000 Aug 15 TI - Dendritic cells containing apoptotic melanoma cells prime human CD8+ T cells for efficient tumor cell lysis. PG - 4446-52 AB - Dendritic cells (DCs) phagocytose apoptotic influenza-infected monocytes and cross-present influenza antigen to CD8+ T cells, generating a specific CTL response. We investigated whether apoptotic melanoma cells, presented by this mechanism, can lead to CTL responses to tumor-associated antigens and melanoma cells. Apoptotic HLA-A2- MEL-397 melanoma cells were internalized by HLA-A2+ immature monocyte-derived DCs but failed to induce maturation of DCs. When exposed to interleukin 6, interleukin 1beta, tumor necrosis factor alpha, and prostaglandin E2, DCs containing apoptotic MEL-397 cell material matured normally [cross-presenting DCs (cp-DCs)]. Autologous CD8+ CTL lines generated with cp-DCs produced tumor necrosis factor when stimulated with HLA-A2-binding immunodominant peptides from MelanA/MART1 and MAGE-3 (expressed by MEL-397 cells) but not tyrosinase (absent in MEL-397). T2 target cells loaded with the respective peptides were lysed by these cell lines, although to a lesser extent than by CTL lines generated in the presence of mature DCs and peptides from melanoma-associated h antigens. In contrast, lines generated with cp-DCs lysed HLA-A2+ MEL-526 melanoma cells or allogenic HLA-A2+ cp-DCs efficiently, whereas the CTL generated with DCs and peptides had little lytic activity. Mature DCs containing apoptotic tumor cells may thus represent an alternative approach for the therapy of malignant tumors. FAU - Jenne, L AU - Jenne L AD - Department of Dermatology, University Hospital Geneva, Switzerland. FAU - Arrighi, J F AU - Arrighi JF FAU - Jonuleit, H AU - Jonuleit H FAU - Saurat, J H AU - Saurat JH FAU - Hauser, C AU - Hauser C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Antigens, Neoplasm) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A2 Antigen) RN - 0 (Immunodominant Epitopes) RN - 0 (MAGEA3 protein, human) RN - 0 (MART-1 Antigen) RN - 0 (MLANA protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Peptide Fragments) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.14.18.1 (Monophenol Monooxygenase) SB - IM MH - Antigen Presentation/*immunology MH - *Antigens, Neoplasm MH - Apoptosis/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Cytotoxicity, Immunologic/immunology MH - Dendritic Cells/*immunology MH - Epitopes, T-Lymphocyte/immunology MH - HLA-A2 Antigen/biosynthesis/immunology MH - Humans MH - Immunodominant Epitopes/immunology MH - Immunotherapy/methods MH - Lymphocyte Activation/immunology MH - MART-1 Antigen MH - Melanoma/*immunology/pathology/therapy MH - Monophenol Monooxygenase/immunology MH - Neoplasm Proteins/immunology MH - Peptide Fragments/immunology MH - Phagocytosis MH - T-Lymphocytes, Cytotoxic/immunology/metabolism MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/immunology/metabolism EDAT- 2000/09/02 11:00 MHDA- 2000/09/19 11:01 CRDT- 2000/09/02 11:00 PHST- 2000/09/02 11:00 [pubmed] PHST- 2000/09/19 11:01 [medline] PHST- 2000/09/02 11:00 [entrez] PST - ppublish SO - Cancer Res. 2000 Aug 15;60(16):4446-52.