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

Publication date: 14 August 2017 Source:Cancer Cell, Volume 32, Issue 2 Author(s): Dipongkor Saha, Robert L. Martuza, Samuel D. Rabkin 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. Graphical abstract Teaser Saha et al. show that the combination of an oncolytic virus expressing IL-12 with two immune checkpoint inhibitors, anti-CTLA-4 and anti-PD1 antibodies, can eradicate glioma in two mouse models. The therapeutic efficacy of the combination treatment depends on CD4+ and CD8+ T cells as well as macrophages.
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research