Inhibition of Myeloperoxidase Enhances Immune Checkpoint Therapy for Melanoma

Authors

Tracy W Liu
Seth T Gammon
Ping Yang
Wencai Ma
Jing Wang
David Piwnica-Worms

Publication Date

2-1-2023

Journal

The Journal for ImmunoTherapy of Cancer

Abstract

BACKGROUND: The presence of a highly immunosuppressive tumor microenvironment has limited the success of immune checkpoint therapy (ICT). Immune suppressing myeloid cells with increased production of reactive oxygen species are critical drivers of this immunosuppressive tumor microenvironment. Strategies to limit these immune suppressing myeloid cells are needed to enhance response to ICT.

METHODS: To evaluate the contribution of myeloperoxidase (MPO), a myeloid lineage-restricted enzyme and a major source of reactive oxygen species, to mediating ICT response, we compared treatment outcome and immune composition in wild-type, MPO-deficient (

RESULTS: Tumor growth and survival studies demonstrated that either host deficiency (

CONCLUSION: MPO contributes to ICT resistance in established melanoma. Repurposing MPO-specific inhibitors may provide a promising therapeutic strategy to enhance ICT response.

Keywords

Animals, Mice, Peroxidase, Reactive Oxygen Species, Melanoma, B-Lymphocytes, Immunity, Innate, Immunosuppressive Agents, Tumor Microenvironment

Comments

Supplementary Materials

Data Availability Statement

PMID: 36805920