Background
Anti- and pro-tumorigenic function of myeloid cells in cancer pathogenesis
Tumor-associated regulatory dendritic cells (TAR-DCs)
Tumor-associated macrophages (TAMs)
Myeloid-derived suppressor cells (MDSCs)
Tumor-associated neutrophils (TANs)
Tumor-promoting myeloid cells and human oncoviral infection
Virus | Oncogene/Oncoprotein Signaling pathway | Downstream consequence |
---|---|---|
Epstein-Barr virus (EBV) | LMP1 | Upregulation of IL-1, IL-6, and GM-CSF MDSC proliferation Increased M2 macrophages Inhibition of NK cell and T-cell |
Hepatitis B virus (HBV) | HBx | Increased M2 macrophages Activation of NKG2D in NK cells T cell senescence |
Hepatitis C virus (HCV) | Core protein | Activation of TLR2/PI3K/AKT/STAT3 signaling cascade Inhibition of CD4 + T cells MDSC proliferation Downregulation of IFN-γ |
Human herpesvirus 8 (HHV-8) | vFLIP | Induction of CD11b + Gr1 + cells MDSC proliferation |
Human papillomavirus (HPV) | E6, E7 | Inhibition of p53, MDSC proliferation Increased Treg cell Downregulation of IFN-γ |
Epstein-Barr virus (EBV)
MDSCs
TAMs
Hepatitis B virus (HBV)
MDSCs
Macrophages
NK cells
Hepatitis C virus (HCV)
Human herpesvirus 8 (HHV-8)
Human papillomavirus (HPV)
Tumor-promoting myeloid cells and potential targets for immunotherapy of human oncoviruses
Mechanism | Molecular and/or Cellular Target | Agent(s) | Reference |
---|---|---|---|
Blocking recruitment | CXCR4/CXCL12 axis | AMD3100 | [125] |
PI3Kγ | IPI-549 | [126] | |
mTORC | Rapalogs | [127] | |
BTK | Ibrutinib | [128] | |
CCR2/CCL2 | Carlumab, C1142, Bindarit | ||
Inhibiting differentiation | CSF1R/CSF1 axis | Emactuzumab (RG7155), Cabiralizumab (FPA008), Pexidartinib, ARRY-382, SNFX-6352, BLZ945, AMG820, IMC-CS4, LY3022855 | |
CD40 activation | CD40 | Selicrelumab, APX005M, SEA-CD40, CP-870-893 | |
TLR activation | TLR1 | Pam3 | [145] |
TLR2 | Pam3-CSK4, SMU-Z1, LTA | ||
TLR3 | Poly:IC | [148] | |
TLR4 | GSK1795091 | [149] | |
TLR6 | LTA | [150] | |
TLR7/8 | NKTR262, Resiquimod, Imiquimod, SM-052 | ||
TLR9 | IMO-2125, CMP-001, SD-101 CpG | ||
Immune checkpoint blockade | SIRPα/CD47 axis | CV1, TTI-621, Hu5F9-G4 | |
MARCO | mAbs (Unknown) | [160] | |
PI3K inhibition | PI3K | SF1126, SRX3207, Clotrimazole | |
HDAC inhibition | HDAC | TMP195 | [116] |
Angiogenesis inhibition | VEGF/VEGFR axis | mAb | [161] |
Apoptosis | TAM | Zoledronate, Trabectedin | |
Inhibition of ATP synthesis | ATP synthase | Oligomycin, 2-Deoxyglucose |