The effects of various OVs on immune cells in the GB tumor microenvironment

OVImmune cellsEffect of OVReference
G47D-mIL-12 (HSV-1)TAMs

  • Recruiting and activating dormant monocytes into M1-like macrophages.

  • Conv Adenovirus erting existing macrophages M2-type TAMs into the macrophages M1 phenotype.

[59]
Delta-24-RGDOX (adenovirus)Tregs

  • IDO expression and Treg activation.

  • Enhanced Ovs’ anti-tumor effects through Treg targeting.

[57, 60]
oHSV (HSV-1)MonocytesRecruitment and polarization of non-activated monocytes into M1-like macrophages.[61]
Poxviral infections (wild vaccinia virus)NK cells and DCsRecruitment and activation of pro-inflammatory M1 macrophages and other innate immune cells like NK cells and DCs.[62]
OV-αCD47-G4 (HSV-1)MacrophagesTransformation of M2 macrophages into the M1 phenotype.[63]
M010 (HSV-1)CytokinesChemoattractants released by OV-infected tumor cells, such as CCL-2 and CCN1, attract TAMs and other immune cells to the tumor site.[64]
oHSV (HSV-1)MDSC

  • Increasing MDSC infiltration.

  • Reprogramming MDSCs from a pro-tumor to an anti-tumor phenotype.

  • The recruitment of MDSCs may depend on virus type, tumor type, and timing.

  • High levels of MDSC infiltration are associated with resistance to OV-mediated anti-tumor effects.

[65]
NDVCD4+ T cells↑ CD8+ T cells↑, MDSCs↓

  • Decreasing MDSC infiltration.

  • Reprogramming MDSCs from a pro-tumor to an anti-tumor phenotype.

  • The recruitment of MDSCs may depend on virus type, tumor type, and timing.

  • High levels of MDSC infiltration are associated with resistance to OV-mediated anti-tumor effects.

[66]
Adenovirus (Delta-24-RGDOX)IFN-γ

  • Induction of a M1-like phenotype in TAMs, particularly around the injection site of the OV.

  • TAMs in this M1-like state can produce IFNs and eliminate viruses through a type I IFN-dependent mechanism.

  • Production of IFN-γ by NK cells in response to the presence of OV.

[67]
oHSV (HSV-1)TNF-αSecretion of TNF-α by TAMs, has been shown to be a crucial factor in inhibiting viral replication by inducing apoptosis in OV-infected glioma cells.[63]

CCL-2: chemokine (C-C motif) ligand-2; CCN1: cellular communication network factor 1; DCs: dendritic cells; GB: glioblastoma; HSV-1: herpes simplex virus type 1; IDO: indoleamine 2,3-dioxygenase; IFN-γ: interferon-gamma; MDSC: myeloid-derived suppressor cell; mIL-12: murine interleukin-12; NDV: Newcastle disease virus; NK: natural killer; oHSV: oncolytic herpes simplex virus; OVs: oncolytic viruses; TAMs: tumor-associated macrophages; TNF-α: tumor necrosis factor-alpha; Tregs: regulatory T cells. ↑: increase ; ↓: decrease