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Intratumoral injection of IFN-β induces chemokine production in melanoma and augments the therapeutic efficacy of anti-PD-L1 mAb.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2017 Aug 19; Vol. 490 (2), pp. 521-527. Date of Electronic Publication: 2017 Jun 15. - Publication Year :
- 2017
-
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 <superscript>+</superscript> 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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Monoclonal administration & dosage
Antibodies, Monoclonal immunology
Antineoplastic Agents administration & dosage
Antineoplastic Agents immunology
Cell Line, Tumor
Chemokine CCL5 analysis
Chemokine CCL5 immunology
Female
Humans
Immunologic Factors administration & dosage
Immunologic Factors immunology
Injections, Intralesional
Interferon-beta administration & dosage
Interferon-beta immunology
Melanoma immunology
Melanoma pathology
Mice
Mice, Inbred C57BL
Receptors, CXCR3 analysis
Receptors, CXCR3 immunology
Antibodies, Monoclonal therapeutic use
Antineoplastic Agents therapeutic use
Immunologic Factors therapeutic use
Interferon-beta therapeutic use
Melanoma drug therapy
Programmed Cell Death 1 Receptor immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 490
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 28624449
- Full Text :
- https://doi.org/10.1016/j.bbrc.2017.06.072