title: Macrophage response to oncolytic paramyxoviruses potentiates virus-mediated tumor cell killing.
abstract: Tumor-associated macrophages (TAMs) are known to regulate tumor response to many anti-cancer therapies, including oncolytic virotherapy. Oncolytic virotherapy employing oncolytic paramyxoviruses, such as attenuated measles (MeV) and mumps (MuV) viruses, has demonstrated therapeutic potential against various malignancies. However, the response of TAMs to oncolytic paramyxoviruses and the consequent effect on virotherapeutic efficacy remains to be characterized. Here, we demonstrate that the presence of human monocyte-derived macrophages (MDMs), irrespective of initial polarization state, enhances the virotherapeutic effect of MeV and MuV on breast cancer cells. Notably, our finding contrasts those of several studies involving other oncolytic viruses, which suggest that TAMs negatively impact virotherapeutic efficacy by impeding virus replication and dissemination. We found that the enhanced virotherapeutic effect in the presence of MDMs was due to slightly delayed proliferation and significantly elevated cell death that was not a result of increased virus replication. Instead, we found that the enhanced virotherapeutic effect involved several macrophage-associated anti-tumor mediators, and was associated with the modulation of MDMs towards an anti-tumor phenotype. Our findings present an alternative view on the role of TAMs in oncolytic virotherapy, and highlight the immunotherapeutic potential of oncolytic paramyxoviruses; possibly contributing towards the overall efficacy of oncolytic virotherapy.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Darren Qiancheng
authors.initials: DQ
authors.lastname: Tan
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: LiFeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohba
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Koji
authors.initials: K
authors.lastname: Ichiyama
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008459:Measles virus / Q000378:metabolism*; D009109:Mumps virus / Q000378:metabolism*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000378:metabolism*; D059016:Tumor Microenvironment; D014779:Virus Replication
keywords: Macrophages; Measles virus; Mumps virus; Oncolytic virotherapy; Tumor microenvironment