Table 1.

Summary of the innate and adaptive immune responses to oncolytic ssRNA(−) viruses

Virus	Innate immune responses	Adaptive immune responses
Newcastle disease virus	Inflammasome activation via NLRP3[15] Type I IFN activation[16,17] Release of DAMPs[18,19] NK activation via HN binding[20,21] DC maturation[18,22] M1 macrophage polarization[22]	Cross-presentation by DC1[22] Increased CD8+/CD4+ T cell infiltration & activation[23,24] Decrease in T-regs[23]
Sendai (HVJ-E)	SAMD9 expression via type-I IFN[25] Stimulates RIG-I/MAVS in cytoplasm, enhancing Noxa and TRAIL via IRF-3 and IRF-7[26] Promotes DC maturation, inducing production of IFN-α (especially IFN-α1a), -β, and -y, TNF-α and IL-6; causes DC tumor infiltration[27] Recognition of viral RNA genome by TLR-7 and -8 in the endosome Activation of NK cells by CXCL-10[28] Removal of sialic acid receptors from cells[29]	IL-6 enhances the proliferation and activation of cytotoxic T-lymphocytes (CTLs) by suppressing the activity of regulatory T-cells (T-regs)[30] Improves presentation of antigens MHC-I and MHC-II[29]
Measles	Increased TRAIL-mediated cytotoxicity by myeloid and plasmacytoid DCs[31] Modulation of macrophages towards an antitumor phenotype through macrophage repolarization[32] Activation of neutrophils (secretion of IL-8, TNF-α, MCP-1, and IFN-α, TRAIL expression, and degranulation)[33] Sensing of viral RNA by PRRs, RIG-I and MDA-5 triggering production of type 1 interferon (IFNα/β)[34] Induction of ISGs involved in anti-viral defense and apoptosis signaling by IFN binding to JAK/STAT pathway[35,36]	Immunogenic cell death[37] Induction of distinctive immunopeptidome[38] Promotion of cross-priming of antitumor T celkesponses by conventional and plasmacytoid dendritic cells[39,40] Enhanced production of IFNa and cross-presenting of tumor antigens to CD8+ T-cells by Plasmacytoid DCs (pDCs)[41] Activation of DCs by upregulating costimulatory surface activation markers CD80 and CD86 [42]
APMV-4	Strong Type I IFN response[43]	Shown to confer immunological memory after complete remission of tumors in vivo[43]
Vesicular stomatitis virus	Infiltration of neutrophils and NK cells[44,45] and induction of type III IFN Mediation of pDC maturation and activation through TLR-7, leading to induction of IFNa and priming of CD8+ T cells[44–46] Induction of type I IFN expression through TLR-4, TLR-3, TLR-7, and TLR-13 and RIG-I[44–48] Upregulation of MHC class II, CD80, CD86, CD40, which all lead to improved antigen presentation, as well as induction of high levels of type I IFNs[49–52] Release of TAAs, PAMPs and DAMPs, induction of ICD markers, such as ecto-CRT, HMGB1, ATP, and Hsp70 and Hsp90[53] Release of IL-28 in TME, tumor cells display NK cell ligands; NK, activation and cytotoxicity[54]	Induction of tumor-specific CD8+ T cells that are induced following the release of tumor-associated antigens[55,56]
Maraba virus MG1	Increased induction of DCs and NK effector cells secreting IFN-γ or granzyme B[57] Increased expression of chemokines like CCL5, CXCL11[58] Production of IFN-γ reliant on the receptor IFN-αR1[58]	Greater infiltration of MG1-infected tumors by T-cells in vivo, a migration dependent on CXCR3, the target receptor of the Th1/Tc1- associated chemokines CXCL9, 10, and 11[59]
Influenza A virus	Induction of PANoptosis[60] M2 to M1 polarization[61] pDC maturation[62] DCs cross-presentation of TAA to CD8+[62]	Cross priming of CD8+ T cells[62] Increased expansion of CD8+ T cells[62]

NLRP3: NOD-, LRR- and pyrin domain-containing protein 3; IFN: interferon; DAMP: damage-associated molecular pattern; NK: natural killer; HN: hemagglutinin-neuraminidase; DC: dendritic cell; M: macrophage; CD: cluster of differentiation; T-regs: regulatory T cells; SAMD9: sterile alpha motif domain-containing protein 9; RIG-I: retinoic acid-inducible gene I; MAVS: mitochondrial antiviral-signaling protein; TRAIL: TNF (tumor necrosis factor)-related apoptosis-inducing ligand; IRF: interferon regulatory factor; TNF-α: tumor necrosis factor alpha; IL-6: interleukin 6; RNA: ribonucleic acid; TLR: toll-like receptor; CXCL: CXC chemokine ligand; CTL: cytotoxic T-lymphocytes; MHC: major histocompatibility complex; MCP-1: monocyte chemoattractant protein-1; CXC: chemokine ligand; PRR: pattern recognition receptor; MDA5: melanoma differentiation-associated protein 5; ISG: interferon-stimulated gene; JAK/STAT: Janus kinase (JAK) - signal transducer and activation of transcription (STAT); pDC: plasmacytoid dendritic cell; TAA: tumor-associated antigen; PAMP: pathogen-associated molecular pattern; ICD: immunogenic cell death; CRT: calreticulin; HMGB1: high mobility group box protein 1; AT: adenosine triphosphate; HSP: heat shock protein; TME: tumor microenvironment; CCL: CC chemokine ligand; IFN-αR1: interferon-alpha receptor 1; Th1: Type 1 helper; Tc1: Type 1 (CD8+) T cells.