Effects of allogeneic hematopoietic stem cell transplantation plus thymus transplantation on malignant tumors: comparison between fetal, newborn, and adult mice.
We have recently shown that allogeneic intrabone marrow-bone marrow transplantation + adult thymus transplantation (TT) is effective for hosts with malignant tumors. However, since thymic and hematopoietic cell functions differ with age, the most effective age for such intervention needed to be determined. We performed hematopoietic stem cell transplantation (HSCT) using the intrabone marrow method with or without TT from fetal, newborn, and adult B6 mice (H-2(b)) into BALB/c mice (H-2(d)) bearing Meth-A sarcoma (H-2(d)). The mice treated with all types of HSCT + TT showed more pronounced regression and longer survival than those treated with HSCT alone in all age groups. Those treated with HSCT + TT showed increased numbers of CD4(+) and CD8(+) T cells but decreased numbers of Gr-1/Mac-1 myeloid suppressor cells and decreased percentages of FoxP3 cells in CD4(+) T cells, compared with those treated with HSCT alone. In all mice, those treated with fetal liver cell (as fetal HSCs) transplantation + fetal TT or with newborn liver cell (as newborn HSCs) transplantation (NLT) + newborn TT (NTT) showed the most regression, and the latter showed the longest survival. The number of Gr-1/Mac-1 cells was the lowest, whereas the percentage of CD62L(-)CD44(+) effector memory T cells and the production of interferon γ (IFN-γ) were highest in the mice treated with NLT + NTT. These findings indicate that, at any age, HSCT + TT is more effective against cancer than HSCT alone and that NLT + NTT is most effective.
Zhang
Yuming
Y
First Department of Pathology, Kansai Medical University, Osaka, Japan.
Hosaka
Naoki
N
Cui
Yunze
Y
Shi
Ming
M
Ikehara
Susumu
S
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D008099:Liver / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000637:transplantation*; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D047368:Tumor Burden
D000945:Antigens, Differentiation, T-Lymphocyte; D039481:CD11b Antigen; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine