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Biochem Biophys Res Commun. 2017 Aug 19;490(2):521-527. doi: 10.1016/j.bbrc.2017.06.072. Epub 2017 Jun 15.

Intratumoral injection of IFN-β induces chemokine production in melanoma and augments the therapeutic efficacy of anti-PD-L1 mAb.

Author information

1
Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan.
2
Department of Pathology, Asahikawa Medical University, Asahikawa, Japan. Electronic address: ohkurit@asahikawa-med.ac.jp.
3
Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
4
Department of Pathology, Asahikawa Medical University, Asahikawa, Japan; Department of Respiratory and Breast Center, Asahikawa Medical University, Asahikawa, Japan.
5
Department of Pathology, Asahikawa Medical University, Asahikawa, Japan; Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
6
Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
7
Department of Pathology, Asahikawa Medical University, Asahikawa, Japan. Electronic address: hiroya@asahikawa-med.ac.jp.

Abstract

Despite recent advances in treatment for melanoma patients through using immune checkpoint inhibitors, these monotherapies have limitations and additional treatments have been explored. Type I IFNs have been used to treat melanoma and possess immunomodulatory effects including enhancement of T-cell infiltration. T-cell plays a critical role in immune checkpoint therapies via restoration of effector functions and tumor infiltration by T-cells predicts longer survival in a variety of cancer types. Moreover, tumor-infiltrating T-cells are associated with the expression of chemokines such as CCL5 and CXCR3 ligands in tumor tissues. We therefore investigated whether intratumoral injection of IFN-β induces the expression of CCL5 and CXCR3 ligands in melanoma cells and has additional antitumor effects when combined with anti-PD-L1 mAb treatment. IFN-β treatment enhanced CD8+ T-cell infiltration into tumors and CCL5 and CXCR3 ligand expression. In vivo studies using a mouse model showed that monotherapy with IFN-β, but not with anti-PD-L1 mAb, inhibited tumor growth in comparison to control. However, the therapeutic efficacy of IFN-β was significantly enhanced by the addition of anti-PD-L1 mAb. This antitumor response of combination therapy was abrogated by anti-CD8 mAb and IFN-β augmented the neoantigen-specific T-cell response of anti-PD-L1 mAb. Our findings suggest that IFN-β induces the expression of CCL5 and CXCR3 ligands in melanoma, which could play a role in T-cell recruitment, and enhances the efficacy of anti-PD-L1 mAb treatment in a CD8-dependent manner.

KEYWORDS:

Chemokine; INF-β; Melanoma; Neoantigen; PD-L1

PMID:
28624449
DOI:
10.1016/j.bbrc.2017.06.072
[Indexed for MEDLINE]

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