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Abstract
The status of humoral immunity of cancer patients is not clear compared to cellular immunity because the ability of specific antibody production is difficult to analyze in vitro. We previously developed a humanized mouse model to evaluate antigen-specific antibody production by transplanting human peripheral blood mononuclear cells (PBMCs) into NOG-hIL-4-Tg mice (hu-PBL hIL-4 NOG). In this study, these mice were transplanted with PBMCs derived from breast cancer patients (BC) and immunized with a human epidermal growth factor receptor 2 (HER2) peptide, CH401MAP, to analyze humoral immunity of BCs. The hu-PBL hIL-4 NOG mice recapitulated immune environment of BCs as the ratio of CD8+/CD4+T cells was lower and that of PD-1 + T cells was higher compared to healthy donors (HDs). Diverse clusters were detected in BC-mouse (BC-M) plasma components involving immunoglobulins and complements unlike HD-M, and there was a significant diversity in CH401MAP-specific IgG titers in BC-M. The number of B cell clones producing high CH401MAP-specific IgG was not increased by immunization in BC-M unlike HD-M. These results demonstrated that the humoral immunity of BCs appeared as diverse phenotypes different from HDs in hu-PBL hIL-4 NOG mice, which may provide important information for the study of personalized medicine.
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1 Tokai University School of Medicine, Division of Basic Medical Science, Department of Molecular Life Science, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); Central Institute for Experimental Animals, Kawasaki, Japan (GRID:grid.452212.2) (ISNI:0000 0004 0376 978X)
2 Tokai University School of Medicine, Division of Basic Medical Science, Department of Molecular Life Science, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
3 Tokai University School of Medicine, Division of Basic Medical Science, Department of Molecular Life Science, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626); Tokai University School of Medicine, Department of Breast and Endocrine Surgery, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
4 Tokyo Metropolitan Institute of Medical Science, Department of Dementia and Higher Brain Function, Tokyo, Japan (GRID:grid.272456.0)
5 Central Institute for Experimental Animals, Kawasaki, Japan (GRID:grid.452212.2) (ISNI:0000 0004 0376 978X)
6 Tokai University School of Medicine, Department of Breast and Endocrine Surgery, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
7 Tokai University School of Medicine, Department of Obstetrics and Gynecology, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
8 Tokai University School of Medicine, Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)
9 Tokai University School of Medicine, Department of Hematology and Oncology, Isehara, Japan (GRID:grid.265061.6) (ISNI:0000 0001 1516 6626)