Examples of nonchemotherapeutic antileukemic agents capable of reinstating the immunogenicity of AML cells
| Drug | Effects on AML Cell Immunogenicity | Effects on DCs (and Other Antitumor Immune Effectors) |
|---|---|---|
| Cytokines (e.g., interferon-α) | • Immunogenic cell death (Rizza et al., 2015) | • ↑ DC activation and function (Anguille et al., 2011b) |
| • ↑ MHC and/or costimulatory molecule expression (Anguille et al., 2011b) | • ↑ direct antileukemic cytotoxicity of DCs (Tel et al., 2014) | |
| • ↑ AML antigen expression expression (Anguille et al., 2011b) | • ↑ activity of T cells and NK cells (Anguille et al., 2011b) | |
| TLR ligands [e.g., poly(I:C), R-848] | • Immunogenic cell death (Smits et al., 2007; Lion et al., 2011) | • ↑ DC activation and function (Smits et al., 2007; Lion et al., 2011) |
| • ↑ MHC and/or costimulatory molecule expression (Smits et al., 2007) | • ↑ activity of T cells and NK cells (Smits et al., 2010) | |
| Hypomethylating drugs (e.g., azacitidine, decitabine) | • Immunogenic cell death (Tang et al., 2013) | • ↑ DC function (Frikeche et al., 2011) |
| • Derepression of AML antigen expression (e.g., CTAs, WT1) (Almstedt et al., 2010; Goodyear et al., 2010; Atanackovic et al., 2011; Kwon et al., 2012; Yao et al., 2013) | • ↑ Treg cells (conflicting data) (Goodyear et al., 2012; Gang et al., 2014) | |
| • ↑ MHC and/or costimulatory molecule expression (Wang et al., 2013) | • ↓ activity of NK cells (Schonefeldt et al., 2013; Gang et al., 2014) | |
| • ↑ NKG2D ligand expression (Rohner et al., 2007) | ||
| Histone deacetylase inhibitors | • Immunogenic cell death (Fredly et al., 2011) | • ↓ DC function (Falkenberg and Johnstone, 2014) |
| • ↑ differentiation of AML cells toward a DC phenotype (Moldenhauer et al., 2004) | • ↑ IDO expression in DCs (Reddy et al., 2008) | |
| • Derepression of AML antigen expression (e.g., CTAs) (Goodyear et al., 2010; Yao et al., 2013) | ||
| • ↑ MHC and/or costimulatory molecule expression (Maeda et al., 2000; Yao et al., 2013) | ||
| • ↑ NKG2D ligand expression (Rohner et al., 2007; Diermayr et al., 2008; Poggi et al., 2009) | ||
| Protein kinase C inhibitor (bryostatin) | • ↑ differentiation of AML cells toward a DC phenotype (Roddie et al., 2002) | • ↑ DC activation and function (Do et al., 2004; Ariza et al., 2011) |
| • ↑ NKG2D ligand expression (Rohner et al., 2007) |
CTAs, cancer-testis antigens.