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.