PMID- 16455969 OWN - NLM STAT- MEDLINE DCOM- 20060314 LR - 20210102 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 176 IP - 4 DP - 2006 Feb 15 TI - Hyperthermia enhances CTL cross-priming. PG - 2134-41 AB - Dendritic cells (DCs) loaded with killed allogeneic melanoma cells can cross-prime naive CD8(+) T cells to differentiate into melanoma-specific CTLs in 3-wk cultures. In this study we show that DCs loaded with killed melanoma cells that were heated to 42 degrees C before killing are more efficient in cross-priming of naive CD8(+) T cells than DCs loaded with unheated killed melanoma cells. The enhanced cross-priming was demonstrated by several parameters: 1) induction of naive CD8(+) T cell differentiation in 2-wk cultures, 2) enhanced killing of melanoma peptide-pulsed T2 cells, 3) enhanced killing of HLA-A*0201(+) melanoma cells in a standard 4-h chromium release assay, and 4) enhanced capacity to prevent tumor growth in vitro in a tumor regression assay. Two mechanisms might explain the hyperthermia-induced enhanced cross-priming. First, heat-treated melanoma cells expressed increased levels of 70-kDa heat shock protein (HSP70), and enhanced cross-priming could be reproduced by overexpression of HSP70 in melanoma cells transduced with HSP70 encoding lentiviral vector. Second, hyperthermia resulted in the increased transcription of several tumor Ag-associated Ags, including MAGE-B3, -B4, -A8, and -A10. Thus, heat treatment of tumor cells permits enhanced cross-priming, possibly via up-regulation of both HSPs and tumor Ag expression. FAU - Shi, Hongzhen AU - Shi H AD - Baylor Institute for Immunology Research, Dallas, TX 75204, USA. FAU - Cao, Tinghua AU - Cao T FAU - Connolly, John E AU - Connolly JE FAU - Monnet, Laurence AU - Monnet L FAU - Bennett, Lynda AU - Bennett L FAU - Chapel, Sylvie AU - Chapel S FAU - Bagnis, Claude AU - Bagnis C FAU - Mannoni, Patrice AU - Mannoni P FAU - Davoust, Jean AU - Davoust J FAU - Palucka, A Karolina AU - Palucka AK FAU - Banchereau, Jacques AU - Banchereau J LA - eng GR - CA085540/CA/NCI NIH HHS/United States GR - CA78846/CA/NCI NIH HHS/United States GR - CA89440/CA/NCI NIH HHS/United States GR - P0-1CA84512/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, Neoplasm) RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - Amino Acid Sequence MH - Antigens, Neoplasm/metabolism MH - Apoptosis MH - Cell Line, Tumor MH - Cross-Priming/*immunology MH - Dendritic Cells/immunology/metabolism MH - Gene Expression Regulation MH - HSP70 Heat-Shock Proteins/chemistry/metabolism MH - Histocompatibility Antigens Class I/metabolism MH - Humans MH - *Hyperthermia, Induced MH - Melanoma/metabolism/pathology MH - Molecular Sequence Data MH - T-Lymphocytes, Cytotoxic/chemistry/*immunology/metabolism MH - Temperature EDAT- 2006/02/04 09:00 MHDA- 2006/03/15 09:00 CRDT- 2006/02/04 09:00 PHST- 2006/02/04 09:00 [pubmed] PHST- 2006/03/15 09:00 [medline] PHST- 2006/02/04 09:00 [entrez] AID - 176/4/2134 [pii] AID - 10.4049/jimmunol.176.4.2134 [doi] PST - ppublish SO - J Immunol. 2006 Feb 15;176(4):2134-41. doi: 10.4049/jimmunol.176.4.2134.