Open AccessActivation of central/effector memory T cells and T‐helper 1 polarization in malignant melanoma patients treated with anti‐ programmed death ‐1 antibody
Author(s) -
Yamaguchi Kyoko,
Mishima Koji,
Ohmura Hirofumi,
Hanamura Fumiyasu,
Ito Mamoru,
Nakano Michitaka,
Tsuchihashi Kenji,
Ota ShunIchiro,
Wada Naoko,
Uchi Hiroshi,
Ariyama Hiroshi,
Kusaba Hitoshi,
Niiro Hiroaki,
Akashi Koichi,
Baba Eishi
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13758
Subject(s) - immune system , cytotoxic t cell , flow cytometry , immunology , melanoma , antibody , peripheral blood mononuclear cell , medicine , cancer research , interleukin 21 , t cell , biology , in vitro , biochemistry
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 CD 8+ T cells with effector memory phenotypes (Tem), and PD ‐1 positive subsets of CD 4+ 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 CD 4+ and CD 8+ 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 CD 3+ CD 4+ CD 45 RO +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 CD 4+ and CD 8+ T cells, but also via a shift to a Th1 phenotype.