PMID- 12234994 OWN - NLM STAT- MEDLINE DCOM- 20021008 LR - 20201215 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 62 IP - 18 DP - 2002 Sep 15 TI - Adenovirus infection enhances dendritic cell immunostimulatory properties and induces natural killer and T-cell-mediated tumor protection. PG - 5260-6 AB - Dendritic cells (DCs) are potent antigen-presenting cells with the potential for cancer immunotherapy. Adenoviral-mediated gene transfer is an attractive means to manipulate the immunostimulatory properties of DCs for therapeutic advantage. Because adenovirus induces DC maturation, we postulated that it would significantly alter their immune functions. Infected DCs markedly increased allogeneic and antigen-specific T-cell proliferation, and augmented natural killer cell lytic activity and IFN-gamma production. The enhanced effector cell stimulation by infected DCs was dependent on their secretion of interleukin 12. Immunization with infected DCs pulsed with tumor antigen protected against flank tumors in 78% of mice and induced a memory response. Antitumor immunity was dependent on both T cells and natural killer cells. Antigen-pulsed, mock-infected DCs were nonprotective. The findings that adenoviral vectors alone critically alter DC immune functions and antitumor properties have important implications for the design and interpretation of immunotherapy regimens using vector-based gene transfer to modulate immunity. FAU - Miller, George AU - Miller G AD - Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. FAU - Lahrs, Svenja AU - Lahrs S FAU - Pillarisetty, Venu G AU - Pillarisetty VG FAU - Shah, Alaap B AU - Shah AB FAU - DeMatteo, Ronald P AU - DeMatteo RP LA - eng GR - CA 94503/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Antigens, Neoplasm) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adenoviridae/*immunology MH - Animals MH - Antigens, Neoplasm/immunology/metabolism MH - Chemotaxis/immunology MH - Coculture Techniques MH - Dendritic Cells/*immunology/virology MH - Immunotherapy, Adoptive/methods MH - Interferon-gamma/biosynthesis/immunology MH - Interleukin-12/biosynthesis/immunology/metabolism MH - Killer Cells, Natural/*immunology MH - Lymphocyte Activation/immunology MH - Lymphoma/immunology/therapy MH - Male MH - Mice MH - Mice, Inbred C57BL MH - T-Lymphocytes/*immunology EDAT- 2002/09/18 10:00 MHDA- 2002/10/09 04:00 CRDT- 2002/09/18 10:00 PHST- 2002/09/18 10:00 [pubmed] PHST- 2002/10/09 04:00 [medline] PHST- 2002/09/18 10:00 [entrez] PST - ppublish SO - Cancer Res. 2002 Sep 15;62(18):5260-6.