Immunomodulatory effect of peritumorally administered interferon-beta on melanoma through tumor-associated macrophages

Aya Kakizaki, Taku Fujimura, Sadanori Furudate, Yumi Kambayashi, Takeshi Yamauchi, Hideo Yagita, Setsuya Aiba

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

An imbalance of immunosuppressive cells and cytotoxic cells plays an important role in the tumor-bearing host. Together with regulatory T cells (Tregs), tumor-associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Since interferon beta (IFN-β) has been clinically used for the treatment of malignant melanoma, we investigated the immunomodulatory effect of IFN-β during melanoma growth to elucidate the effects of IFN-β on the tumor microenvironment by using the B16F10 melanoma model. Peritumorally administered IFN-β significantly decreased the mRNA expression and production of Th2-related chemokines, which suppressed the recruitment of Tregs in B16F10 melanoma. Since the administration of IFN-β augments the expression of PD-1 on TILs, the co-administration of anti-PD-1 Ab augmented the therapeutic effect of IFN-β for the treatment of B16F10 melanoma. Moreover, in parallel with the mouse model, in the human system, IFN-β decreased the production of Th2-related chemokines and augmented the production of Th1-related chemokines from monocyte-derived M2 macrophages. Since these immunomodulatory effects of IFN-β on macrophages were also observed in the lesional skin of human in-transit melanoma, our present data suggest one of the possible immunomodulatory effects of IFN-β and support the possibility of IFN-β in combination with anti-PD-1 Ab for the treatment of melanoma.

Original languageEnglish
JournalOncoImmunology
Volume4
Issue number11
DOIs
Publication statusPublished - 2015 Nov 2

Keywords

  • IFN-β
  • PD-1
  • in-transit melanoma
  • regulatory T cells
  • tumor-associated macrophages

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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