Oncolytic virus immunotherapy: future prospects for oncology

Raja, Junaid; Ludwig, Johannes M.; Gettinger, Scott N.; Schalper, Kurt A.; Kim, Hyun S.

doi:10.1186/s40425-018-0458-z

Table 1 Common tumor escape associated changes

From: Oncolytic virus immunotherapy: future prospects for oncology

Molecule	Full Name	Level of Effect	Type of Disruption	Consequence	Ref
MHC	Major Histocompatibility Complex	Tumor	Downregulation	T cell anergy as costimulatory signal for epitope imprinting factor not presented to T cells	[31,32,33, 43]
TRAIL	Tumor Necrosis Factor Related Apoptosis Inducing Ligand	Tumor	Downregulation	Induction of NK cell apoptosis by TRAIL-R2 binding	[31, 32, 38, 39, 43]
FAS	CD95	Tumor	Downregulation	Inability to induce TNF superfamily mediated apoptosis	[31, 32, 37, 48]
HLA-E	Human Leukocyte Antigen E	Tumor	Upregulation	Binding to inhibitory receptor CD94/NKG2A on NK and CD8⁺ cells	[32, 44]
TGFβ	Transforming Growth Factor Beta	Tumor	Upregulation	Inhibition of CD8⁺ T cell and NK cell proliferation and differentiation and disruption of T cell stimulation by antigen presenting cells	[32, 34,35,36]
VEGF	Vascular Endothelial Growth Factor	Tumor	Upregulation	Inhibition of NK κ B mediated dendritic cell differentiation	[32, 43, 49]
IL 10	Interleukin 10	Tumor	Upregulation	Inhibition of dendritic cell differentiation and tumor cell TAP 1 and 2 production as well as CD4⁺ inhibition	[32, 42, 43]
FLIP	FLICE Inhibitory Pathway	Tumor	Upregulation	Inhibition of death receptor mediated apoptosis by caspase 8 and FADD binding	[32, 37]
CD47	Integrin Associated Protein	Tumor	Upregulation	Signal regulatory protein alpha stimulation within macrophages for ‘don’t eat me’ signal	[31]
Bcl X_L	B Cell Lymphoma Extra Large	Tumor	Upregulation	Inhibition of TRAIL pathway and CD 95 mediated apoptosis	[32, 38]
IFNγ	Interferon Gamma	Tumor	Downregulation	Loss of STAT1 activation and resultant MHC production	[21, 31, 39, 41, 43]
IFNγ	Interferon Gamma	Niche	Upregulation	Induction of PDL1 production to induce T cell deactivation	[21, 31, 41, 43]
iMCs	Immature Myeloid Cells	Niche	Upregulation	Induction of T cell apoptosis, inhibition of T cell proliferation, induction of regulatory phenotype	[32]
Type II Mφ	Type II Macrophages	Niche	Upregulation	Disrupt Th1 immunity, promote angiogenesis and repair mechanisms	[21, 32, 45]
IDO	Indoleamine 2,3-dioxygenase	Immune	Upregulation	Suppression of activated cytotoxic T cells and induction of regulatory T cells	[30, 32, 50]
CD4⁺CD25⁺ T_reg	Regulatory T Cells	Immune	Upregulation	Prevention of activation for CD4⁺, CD8⁺, and NK T cells	[35, 40]
CD1d restricted T cell	Type II Natural Killer T Cells	Immune	Upregulation	Suppression of cytotoxic T cell differentiation via TGFβ production	[32, 40]
PDL1	Programmed Death Ligand 1 or B7-H1	Immune	Upregulation	Induction of T cell apoptosis by binding of PD1	[32, 41]

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