Human allogeneic and murine xenogeneic dendritic cells are cytotoxic to human tumor cells via two distinct pathways.
Human monocyte-derived dendritic cells (DCs), stimulated with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 1 week, major histocompatibility complex killed human tumor cells in 24-hour cytotoxicity assays. These immature DCs were >90% CD11c, major histocompatibility complex class II(+), but <1% were CD83(+) cells. Within 24 hours, these DCs ingested tumor membranes. The DC cells also lysed Jurkat lymphoma cells, but not Jurkat cells genetically knocked out of the Fas-associated death domain (FADD) or caspase-8. DC2.4, a cloned murine DC line, also displayed cytotoxicity toward U-251 cells, although these murine DCs were less potent than human DC. DC2.4 did not kill Jurkat cells, rat T9 glioma cells, or human Caco-2 colon cancer cells, suggesting that a unique receptor or ligand interaction exists between the DC and U-251 cells. This interaction was destroyed by the paraformaldehyde fixation of the tumor cells. Supernatants from the cultures of DC2.4 and tumor cells were analyzed by the Griess reaction for signs of nitric oxide (NO) production. Augmented NO production occurred in DC2.4/U-251 and DC2.4/Jurkat cultures but was not seen in the human DC/U-251 cultures. These studies suggest that DCs possess different mechanisms of tumoricidal activity.
Schiltz
Patric M
PM
Hoag Hospital Memorial Presbyterian Hospital Comprehensive Cancer Center, Newport Beach, CA 92658, USA.
Lee
Gregory J
GJ
Zhang
Jian Gang
JG
Hoa
Neil
N
Wepsic
H Terry
HT
Dillman
Robert O
RO
Jadus
Martin R
MR
D056769:Alstrom Syndrome; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018938:Caco-2 Cells; D053181:Caspase 8 / Q000235:genetics; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000172:deficiency / Q000235:genetics; D005557:Formaldehyde / Q000494:pharmacology; D015870:Gene Expression / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D019169:Jurkat Cells; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D005557:Formaldehyde; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D053181:Caspase 8