title: Immunomodulatory effect of peritumorally administered interferon-beta on melanoma through tumor-associated macrophages.
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.
authors.affiliation: Department of Dermatology; Tohoku University Graduate School of Medicine ; Sendai, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kakizaki
authors.affiliation: Department of Dermatology; Tohoku University Graduate School of Medicine ; Sendai, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Dermatology; Tohoku University Graduate School of Medicine ; Sendai, Japan.
authors.forename: Sadanori
authors.initials: S
authors.lastname: Furudate
authors.affiliation: Department of Dermatology; Tohoku University Graduate School of Medicine ; Sendai, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kambayashi
authors.affiliation: Department of Dermatology; Tohoku University Graduate School of Medicine ; Sendai, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamauchi
authors.affiliation: Department of Immunology; Juntendo University School of Medicine ; Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Department of Dermatology; Tohoku University Graduate School of Medicine ; Sendai, Japan.
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
keywords: IFN-β; PD-1; in-transit melanoma; regulatory T cells; tumor-associated macrophages