Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade.

Authors:
Dipongkor Saha
Dipongkor Saha
Ghent University
Belgium
Robert L Martuza
Robert L Martuza
Massachusetts General Hospital and Harvard Medical School
Samuel D Rabkin
Samuel D Rabkin
Massachusetts General Hospital and Harvard Medical School
Boston | United States

Cancer Cell 2017 08;32(2):253-267.e5

Molecular Neurosurgery Laboratory and the Brain Tumor Research Center, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Department of Neurosurgery, Harvard Medical School, Boston, MA, USA. Electronic address:

Glioblastoma is an immunosuppressive, fatal brain cancer that contains glioblastoma stem-like cells (GSCs). Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells while inducing anti-tumor immunity. oHSV G47Δ expressing murine IL-12 (G47Δ-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly extended survival of a mouse glioma model. However, the triple combination of anti-CTLA-4, anti-PD-1, and G47Δ-mIL12 cured most mice in two glioma models. This treatment was associated with macrophage influx and M1-like polarization, along with increased T effector to T regulatory cell ratios. Immune cell depletion studies demonstrated that CD4 and CD8 T cells as well as macrophages are required for synergistic curative activity. This combination should be translatable to the clinic and other immunosuppressive cancers.

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http://dx.doi.org/10.1016/j.ccell.2017.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568814PMC
August 2017
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