Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages

Taku Fujimura, Aya Kakizaki, Yumi Kambayashi, Yota Sato, Kayo Tanita, Chunbing Lyu, Sadanori Furudate, Setsuya Aiba

研究成果: Article査読

13 被引用数 (Scopus)

抄録

Together with regulatory T cells (Tregs), tumor-associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Although cytotoxic antimelanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU) and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. As the majority of TAMs are alternatively activated M2 macrophages that favour tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte-derived M2 macrophages. First, mRNA expressions and protein production of immune checkpoint molecules, PD-L1 and chemokines by CD163 + CD206 + M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC, ACNU, and VCR. DTIC and VCR significantly decreased PD-L1 mRNA expression, which was confirmed by flow cytometry. Moreover, the mRNA expression and production of CCL22 were significantly decreased by DTIC, which suggested that DTIC might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD-L1 and production of CCL22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T-cell proliferation. The present report suggests one of the possible antimelanoma mechanisms of DAV combination chemotherapy for melanoma patients.

本文言語English
ページ(範囲)64-70
ページ数7
ジャーナルExperimental Dermatology
27
1
DOI
出版ステータスPublished - 2018 1

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 皮膚病学

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