Changes in cellular composition induced by neocarzinostatin pretreatment in Meth A-bearing mice and the responsible antitumor effector cells.
We previously reported that tumor eradication was induced by a single injection of neocarzinostatin (NCS) between 1 day and 4 weeks before Meth A transplantation in Balb/c mice via augmenting host-mediated antitumor activity. In order to elucidate the mechanism of this tumor eradication, the cellular components of spleen and regional lymph nodes, tumor infiltrating cells and antitumor effector cells were investigated. Pretreatment with NCS on day -3 caused an increase in the percentage of T-cell subsets, a decrease in the percentage of B-cells, Mac-1+ cells and asialo GM1+ cells and a decrease of the total cell number in the spleen. These changes were observed before but not during the period of tumor regression and were also observed in non-transplanted mice with NCS treatment. In the lymph nodes, while B-cells increased on Meth A transplantation, this was suppressed by NCS pretreatment. Although histological examination of tumor nodules showed the presence of only a few host immune cells in the tumor tissue, the area of necrosis was already extensive on day 7 and expanded thereafter. In vivo depletion of whole T-cells, T-cell subsets or asialo GM1+ cells by antibody treatment suggests that the antitumor effector cells in tumor eradication were Thy1,2+/Lyt2+, and at least some of which also express asialo GM1 antigen and that L3T4+ T-cells were also involved in tumor eradication.
Masuda
E
E
Molecular Medicine Research Laboratories, Yamanouchi Pharmaceutical Co., Ibaraki, Japan. emasuda@yam-res.co.uk
Shishido
T
T
Fujimoto
R
R
Maeda
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002273:Carcinogens; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; D008748:Methylcholanthrene; D009353:Zinostatin