Activation of central/effector memory T cells and T-helper 1 polarization in malignant melanoma patients treated with anti-programmed death-1 antibody

Kyoko Yamaguchi, Koji Mishima, Hirofumi Ohmura, Fumiyasu Hanamura, Mamoru Ito, Michitaka Nakano, Kenji Tsuchihashi, Shun Ichiro Ota, Naoko Wada, Hiroshi Uchi, Hiroshi Ariyama, Hitoshi Kusaba, Hiroaki Niiro, Koichi Akashi, Eishi Baba

研究成果: ジャーナルへの寄稿記事

9 引用 (Scopus)

抄録

Human anti-programmed death-1 (PD-1) antibody possesses the capability to revitalize host T cells and has been an effective therapy for metastatic malignant melanoma (MM). The precise subsets of T cells predominantly activated by anti-PD-1, however, have not yet been clarified. In this study, peripheral blood mononuclear cells obtained from MM patients scheduled to receive anti-PD-1 (nivolumab) therapy, and healthy subjects (HS), were systematically examined on flow cytometry to identify changes in the proportion of immune cell subsets. Compared with HS, MM patients prior to therapy had an increased proportion of activated CD8+ T cells with effector memory phenotypes (Tem), and PD-1 positive subsets of CD4+ central memory T cells (Tcm) and T-helper (Th)17 cells. After a single course of anti-PD-1 therapy, MM patients had an increase in activated Tem and Tcm subsets of CD4+ and CD8+ T cells, and activated Th1 plus T-helper follicular 1 cells. There was no consistent change in the proportion of Tfh cells, B cells, natural killer cells, or dendritic cells. The observed activated phenotypes were attenuated during the course of therapy, but regulatory T cells belonging to the CD3+CD4+CD45RO+CD25high fraction increased at disease progression. Taken together, anti-PD-1 therapy modulates systemic immune reactions and exerts anti-tumor effects, not only by revitalizing Tem and Tcm of CD4+ and CD8+ T cells, but also via a shift to a Th1 phenotype.

元の言語英語
ページ(範囲)3032-3042
ページ数11
ジャーナルCancer Science
109
発行部数10
DOI
出版物ステータス出版済み - 10 2018

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Th1 Cells
Melanoma
T-Lymphocytes
Antibodies
Phenotype
Healthy Volunteers
Therapeutics
Th17 Cells
T-Lymphocyte Subsets
Regulatory T-Lymphocytes
Natural Killer Cells
Dendritic Cells
Disease Progression
Blood Cells
Flow Cytometry
B-Lymphocytes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Activation of central/effector memory T cells and T-helper 1 polarization in malignant melanoma patients treated with anti-programmed death-1 antibody. / Yamaguchi, Kyoko; Mishima, Koji; Ohmura, Hirofumi; Hanamura, Fumiyasu; Ito, Mamoru; Nakano, Michitaka; Tsuchihashi, Kenji; Ota, Shun Ichiro; Wada, Naoko; Uchi, Hiroshi; Ariyama, Hiroshi; Kusaba, Hitoshi; Niiro, Hiroaki; Akashi, Koichi; Baba, Eishi.

:: Cancer Science, 巻 109, 番号 10, 10.2018, p. 3032-3042.

研究成果: ジャーナルへの寄稿記事

Yamaguchi, Kyoko ; Mishima, Koji ; Ohmura, Hirofumi ; Hanamura, Fumiyasu ; Ito, Mamoru ; Nakano, Michitaka ; Tsuchihashi, Kenji ; Ota, Shun Ichiro ; Wada, Naoko ; Uchi, Hiroshi ; Ariyama, Hiroshi ; Kusaba, Hitoshi ; Niiro, Hiroaki ; Akashi, Koichi ; Baba, Eishi. / Activation of central/effector memory T cells and T-helper 1 polarization in malignant melanoma patients treated with anti-programmed death-1 antibody. :: Cancer Science. 2018 ; 巻 109, 番号 10. pp. 3032-3042.
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abstract = "Human anti-programmed death-1 (PD-1) antibody possesses the capability to revitalize host T cells and has been an effective therapy for metastatic malignant melanoma (MM). The precise subsets of T cells predominantly activated by anti-PD-1, however, have not yet been clarified. In this study, peripheral blood mononuclear cells obtained from MM patients scheduled to receive anti-PD-1 (nivolumab) therapy, and healthy subjects (HS), were systematically examined on flow cytometry to identify changes in the proportion of immune cell subsets. Compared with HS, MM patients prior to therapy had an increased proportion of activated CD8+ T cells with effector memory phenotypes (Tem), and PD-1 positive subsets of CD4+ central memory T cells (Tcm) and T-helper (Th)17 cells. After a single course of anti-PD-1 therapy, MM patients had an increase in activated Tem and Tcm subsets of CD4+ and CD8+ T cells, and activated Th1 plus T-helper follicular 1 cells. There was no consistent change in the proportion of Tfh cells, B cells, natural killer cells, or dendritic cells. The observed activated phenotypes were attenuated during the course of therapy, but regulatory T cells belonging to the CD3+CD4+CD45RO+CD25high fraction increased at disease progression. Taken together, anti-PD-1 therapy modulates systemic immune reactions and exerts anti-tumor effects, not only by revitalizing Tem and Tcm of CD4+ and CD8+ T cells, but also via a shift to a Th1 phenotype.",
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AU - Yamaguchi, Kyoko

AU - Mishima, Koji

AU - Ohmura, Hirofumi

AU - Hanamura, Fumiyasu

AU - Ito, Mamoru

AU - Nakano, Michitaka

AU - Tsuchihashi, Kenji

AU - Ota, Shun Ichiro

AU - Wada, Naoko

AU - Uchi, Hiroshi

AU - Ariyama, Hiroshi

AU - Kusaba, Hitoshi

AU - Niiro, Hiroaki

AU - Akashi, Koichi

AU - Baba, Eishi

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AB - Human anti-programmed death-1 (PD-1) antibody possesses the capability to revitalize host T cells and has been an effective therapy for metastatic malignant melanoma (MM). The precise subsets of T cells predominantly activated by anti-PD-1, however, have not yet been clarified. In this study, peripheral blood mononuclear cells obtained from MM patients scheduled to receive anti-PD-1 (nivolumab) therapy, and healthy subjects (HS), were systematically examined on flow cytometry to identify changes in the proportion of immune cell subsets. Compared with HS, MM patients prior to therapy had an increased proportion of activated CD8+ T cells with effector memory phenotypes (Tem), and PD-1 positive subsets of CD4+ central memory T cells (Tcm) and T-helper (Th)17 cells. After a single course of anti-PD-1 therapy, MM patients had an increase in activated Tem and Tcm subsets of CD4+ and CD8+ T cells, and activated Th1 plus T-helper follicular 1 cells. There was no consistent change in the proportion of Tfh cells, B cells, natural killer cells, or dendritic cells. The observed activated phenotypes were attenuated during the course of therapy, but regulatory T cells belonging to the CD3+CD4+CD45RO+CD25high fraction increased at disease progression. Taken together, anti-PD-1 therapy modulates systemic immune reactions and exerts anti-tumor effects, not only by revitalizing Tem and Tcm of CD4+ and CD8+ T cells, but also via a shift to a Th1 phenotype.

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