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

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 transplantin...

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Autores principales:	Yusuke Ohno, Shino Ohshima, Asuka Miyamoto, Fuyuki Kametani, Ryoji Ito, Banri Tsuda, Yukie Kasama, Shunsuke Nakada, Hirofumi Kashiwagi, Toshiro Seki, Atsushi Yasuda, Kiyoshi Ando, Mamoru Ito, Yutaka Tokuda, Yoshie Kametani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/baa11549f1a649bd983569966cfc7f74
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spelling	oai:doaj.org-article:baa11549f1a649bd983569966cfc7f742021-12-02T16:04:19ZHER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice10.1038/s41598-021-92311-y2045-2322https://doaj.org/article/baa11549f1a649bd983569966cfc7f742021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92311-yhttps://doaj.org/toc/2045-2322Abstract 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.Yusuke OhnoShino OhshimaAsuka MiyamotoFuyuki KametaniRyoji ItoBanri TsudaYukie KasamaShunsuke NakadaHirofumi KashiwagiToshiro SekiAtsushi YasudaKiyoshi AndoMamoru ItoYutaka TokudaYoshie KametaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yusuke Ohno Shino Ohshima Asuka Miyamoto Fuyuki Kametani Ryoji Ito Banri Tsuda Yukie Kasama Shunsuke Nakada Hirofumi Kashiwagi Toshiro Seki Atsushi Yasuda Kiyoshi Ando Mamoru Ito Yutaka Tokuda Yoshie Kametani HER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice
description	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.
format	article
author	Yusuke Ohno Shino Ohshima Asuka Miyamoto Fuyuki Kametani Ryoji Ito Banri Tsuda Yukie Kasama Shunsuke Nakada Hirofumi Kashiwagi Toshiro Seki Atsushi Yasuda Kiyoshi Ando Mamoru Ito Yutaka Tokuda Yoshie Kametani
author_facet	Yusuke Ohno Shino Ohshima Asuka Miyamoto Fuyuki Kametani Ryoji Ito Banri Tsuda Yukie Kasama Shunsuke Nakada Hirofumi Kashiwagi Toshiro Seki Atsushi Yasuda Kiyoshi Ando Mamoru Ito Yutaka Tokuda Yoshie Kametani
author_sort	Yusuke Ohno
title	HER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice
title_short	HER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice
title_full	HER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice
title_fullStr	HER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice
title_full_unstemmed	HER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice
title_sort	her2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-pbl hil-4 nog mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/baa11549f1a649bd983569966cfc7f74
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HER2-antigen-specific humoral immune response in breast cancer lymphocytes transplanted in hu-PBL hIL-4 NOG mice

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