Hyperthermia enhances CTL cross-priming.
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.
Shi
Hongzhen
H
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
Cao
Tinghua
T
Connolly
John E
JE
Monnet
Laurence
L
Bennett
Lynda
L
Chapel
Sylvie
S
Bagnis
Claude
C
Mannoni
Patrice
P
Davoust
Jean
J
Palucka
A Karolina
AK
Banchereau
Jacques
J
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D006979:Hyperthermia, Induced; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013696:Temperature
D000951:Antigens, Neoplasm; D018840:HSP70 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I