HER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice

• Published in: Scientific reports Vol. 11; no. 1; p. 12798
• Main Authors: Ohno, Yusuke, Ohshima, Shino, Miyamoto, Asuka, Kametani, Fuyuki, Ito, Ryoji, Tsuda, Banri, Kasama, Yukie, Nakada, Shunsuke, Kashiwagi, Hirofumi, Seki, Toshiro, Yasuda, Atsushi, Ando, Kiyoshi, Ito, Mamoru, Tokuda, Yutaka, Kametani, Yoshie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647; 631/1647/334; 631/1647/334/1874; 631/1647/334/1874/345; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Neoplasm - metabolism; Antibody Formation - drug effects; Antibody Formation - immunology; Antigens; Antigens, Neoplasm - metabolism; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Blood Proteins - metabolism; Breast cancer; Breast Neoplasms - immunology; Breast Neoplasms - pathology; CD4 antigen; CD8 antigen; Cell-mediated immunity; Epidermal growth factor; ErbB-2 protein; Female; Humanities and Social Sciences; Humans; Humoral immunity; Immune response; Immune response (humoral); Immunity, Humoral - drug effects; Immunization; Immunoglobulin G; Interleukin-4 - metabolism; Leukocytes (mononuclear); Lymphocytes; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes T; Mice; Middle Aged; multidisciplinary; Nivolumab - pharmacology; PD-1 protein; Peripheral blood mononuclear cells; Phenotypes; Precision medicine; Programmed Cell Death 1 Receptor - metabolism; Receptor, ErbB-2 - metabolism; Science; Science (multidisciplinary); Spleen - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tissue Donors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-92311-y

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.