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Updated: Jun 23, 2026
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Quantitative Proteome Responses to Oncolytic Reovirus in GM-CSF- and M-CSF-Differentiated Bone Marrow-Derived Cells
Michael A Giacomantonio1, Andra M Sterea2, Youra Kim1
1Department of Pathology , Dalhousie University , Halifax , Nova Scotia B3H 4R2 , Canada.
Abstract:
The efficacy of oncolytic viruses (OVs), such as reovirus, is dictated by host immune responses, including those mediated by the pro- versus anti-inflammatory macrophages. As such, a detailed understanding of the interaction between reovirus and different macrophage types is critical for therapeutic efficacy. To explore reovirus-macrophage interactions, we performed tandem mass tag (TMT)-based quantitative temporal proteomics on mouse bone marrow-derived macrophages (BMMs) generated with two cytokines, macrophage colony stimulating factor (M-CSF) and granulocytic-macrophage colony stimulating factor (GM-CSF), representing anti- and proinflammatory macrophages, respectively. We quantified 6863 proteins across five time points in duplicate, comparing M-CSF (M-BMM) and GM-CSF (GM-BMM) in response to OV. We find that GM-BMMs have lower expression of key intrinsic proteins that facilitate an antiviral immune response, express higher levels of reovirus receptor protein JAM-A, and are more susceptible to oncolytic reovirus infection compared to M-BMMs. Interestingly, although M-BMMs are less susceptible to reovirus infection and subsequent cell death, they initiate an antireovirus adaptive T cell immune response comparable to that of GM-BMMs. Taken together, these data describe distinct proteome differences between these two macrophage populations in terms of their ability to mount antiviral immune responses.
Insights
Oncolytic virus therapy efficacy depends on macrophage immune responses. GM-CSF-derived macrophages are more susceptible to reovirus, while M-CSF-derived macrophages initiate comparable T cell responses despite lower susceptibility.
Area of Science:
- Immunology
- Virology
- Proteomics
Background:
- Oncolytic viruses (OVs) are promising cancer therapeutics.
- Host immune responses, particularly macrophage polarization, significantly impact OV efficacy.
- Understanding reovirus interactions with distinct macrophage subsets is crucial for optimizing OV therapy.
Purpose of the Study:
- To investigate the differential proteomic responses of anti-inflammatory (M-CSF derived) and pro-inflammatory (GM-CSF derived) macrophages to oncolytic reovirus.
- To elucidate the molecular mechanisms underlying reovirus susceptibility and immune response initiation in different macrophage populations.
Main Methods:
- Quantitative temporal proteomics using tandem mass tag (TMT) labeling.
- Analysis of mouse bone marrow-derived macrophages (BMMs) differentiated with M-CSF or GM-CSF.
- Comparison of proteomes across five time points post-reovirus infection.
Main Results:
- GM-CSF-derived macrophages (GM-BMMs) exhibit lower expression of antiviral proteins and higher reovirus receptor (JAM-A) expression, leading to increased susceptibility.
- M-CSF-derived macrophages (M-BMMs) show reduced susceptibility to reovirus infection and cell death.
- Despite lower susceptibility, M-BMMs mount an adaptive T cell immune response comparable to GM-BMMs.
Conclusions:
- Distinct proteomic profiles dictate the differential response of M-BMMs and GM-BMMs to oncolytic reovirus.
- Macrophage polarization influences susceptibility to viral infection and the subsequent immune response.
- These findings provide critical insights into tailoring OV therapy based on host immune cell characteristics.
