Increased survival and decreased tumor size due to intratumoral injection of ethanol followed by administration of immature dendritic cells.
Antigen-presenting dendritic cells (DC), loaded in vitro with tumor associated antigens (TAAs), are now used for antitumor therapy. However, little is known about the interaction between DC and TAAs within tumor microenvironment. This study was conducted to evaluate if antitumor immunity can be induced by injecting immature DC into necrotized tumor tissues. A mouse model of colon cancer was established by subcutaneous injection of CMT-93 (a murine colon cancer cell) in the flank of C57BL/6 mice. When the tumors became about 10 mm in diameter, a portion of the tumor nodules was necrotized by injecting 100 micro l of 100% ethanol. Bone marrow-derived immature DC from syngenic mice were injected into the tumors, 48 h after ethanol injection. The size of the tumor and the survival time of the mice were studied. Immunohistochemical methodology was employed to detect injected DC and to evaluate the levels of maturation of DC. Tumor-bearing mice injected with ethanol plus DC survived for longer duration compared to untreated mice (p<0.05). Three weeks after therapy, the sizes of the tumor nodules were reduced compared to untreated mice. Forty-eight hours after injection, the injected DC were detected in the spleen. The stimulatory capacity of spleen DC isolated from mice treated with ethanol plus DC were significantly higher compared to that of untreated mice (p<0.05). Mature DC expressing CD86 were detected in cancer nodule after injecting ethanol plus DC, however, these were almost absent in tumor-bearing mice in situ. Taken together, direct administration of ethanol plus DC in the tumor nodules represents a new therapeutic approach for antitumor immunotherapy.
Kumagi
Teru
T
Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan.
Akbar
S M Fazle
SM
Horiike
Norio
N
Onji
Morikazu
M
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen; D001854:Bone Marrow Cells / Q000166:cytology; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D007150:Immunohistochemistry; D007167:Immunotherapy; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D002492:Central Nervous System Depressants; D008562:Membrane Glycoproteins; D000431:Ethanol