title: The maturation of murine bone marrow-derived dendritic cells by tumor lysate uptake in vitro is not essential for cancer immunotherapy.
abstract: Immunization of dendritic cells (DC) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) which are responsible for protection from tumor challenge and regression of established metastatic tumor. It has been hypothesized that tumor lysate contains factors that may modulate DC maturation. In this study, we examined whether the uptake of tumor lysate (MCA-102 fibrosarcoma) could modulate DC phenotypes in vitro and whether the administration in vivo of tumor lysate-pulsed DC (TP-DC) could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. It was investigated the uptake of tumor lysate by DC by means of flow cytometry and fluorescent microscope. Murine bone marrow-derived DC efficiently phagocytosed tumor lysate and after the uptake, the phenotype of TP-DC was surprisingly comparable to unpulsed-DC (UP-DC), exhibiting lower levels of CD80 (<51%), CD86 (<43%), and MHC class II (<59%). Also, TP-DC did not enhance secretion of IL-12p70 (UP- vs. TP; 54.5+/-6.4 vs. 50.5+/-4.8 pg/ml, respectively), contrary to those activated with LPS (113.6+/-16.8 pg/ml). However, TP-DC vaccination in vivo increased the IFN-gamma production from splenocytes higher than that of UP-DC (TP- vs. UP-DC; 41029+/-1523 vs. 4752+/-590 pg/ml, respectively). Furthermore, the administration of TP-DC enhanced specific T cell responses against MCA-102 fibrosarcoma. These results demonstrate that augmentation of DC phenotype and function in vitro is not necessarily a prerequisite for TP-DC vaccination to successfully promote anti-tumor immunity in vivo.
authors.affiliation: Department of Microbiology and Immunology, National Research Laboratory of Dendritic Cell Differentiation and Regulation, Medical Research Institute, Busan, Korea.
authors.forename: Sung-Chil
authors.initials: SC
authors.lastname: Woo
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Hyung-Keun
authors.initials: HK
authors.lastname: Kim
authors.forename: Tae-Hyung
authors.initials: TH
authors.lastname: Lee
authors.forename: Yu-Seok
authors.initials: YS
authors.lastname: Moon
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Park
authors.forename: Man-Soo
authors.initials: MS
authors.lastname: Yoon
authors.forename: Kyu-Sub
authors.initials: KS
authors.lastname: Lee
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005354:Fibrosarcoma / Q000276:immunology* / Q000473:pathology; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D007371:Interferon-gamma