Table 2. Differences between human and mice immune systems and their effect on the crucial components of immunogenic cell death (ICD).
| Immune system component | Effect on ICD | Mouse immune system | Human immune system | Refs. |
|---|---|---|---|---|
| Caspase-1 and NLRP3 | Caspase-1 and NLRP3 are components of the inflammasome complex. The inflammasome complex is important for vaccination and chemotherapeutic response to ICD; the importance of this effect was characterized in Casp1 and Nlrp3 KO-mice | Mice possess inflammatory caspases like casp-1, -11 and -12 | Humans possess inflammatory caspases like casp-1, -4 and -5; humans possess a non-functional casp-12 | 2, 122 |
| Unlike human NLRP1, murine NLRP1 lacks a functional pyrin domain thereby exhibiting inability to interact with ASC; a number of (mostly negative) human inflammasome regulators like POPs-1/-2, COP, INCA and iceberg do not have corresponding mice orthologs | ||||
| CXCR3 | Receptor for chemokines like Cxcl10, Cxcl9 and Cxcl11; important for vaccination and chemotherapeutic response to ICD; effect characterized in Cxcr3 KO-mice | — | — | 2 |
| IFN-γ and IFN-γ receptor | The type II IFN system is crucial for the vaccination and chemotherapeutic response to ICD; effect characterized in Ifng and Ifngr1 KO-mice | Cultured Th cells produce either IFN-γ or IL-4 | Cultured Th cells produce sometimes both IFN-γ and IL-4 | 2, 65 |
| IL-17A and IL-17A receptor | The IL-17A system is crucial for the vaccination and chemotherapeutic response to ICD; effect characterized in Il17a and Il17ra KO-mice | In mice, IL-6 and TGF-β control the differentiation of IL-17A producing Th17 cells | In humans, IL-1, IL-6 and IL-23 are the key to controlling differentiation of IL-17A producing Th17 cells | 2, 65, 123 |
| IL-1β and IL-1 receptor | The IL-1β-IL-1 receptor system is crucial for the vaccination and chemotherapeutic response to ICD; effect characterized in Il1r1 KO-mice and via neutralization by anti-IL-1β antibodies | — | — | 2 |
| Ly96, MyD88 and TLR4 | The TLR4 signalling system is crucial for the vaccination and chemotherapeutic response to ICD; effect characterized in Ly96, Myd88 and Tlr4 KO-mice, respectively | In mice, TLR4 confers a response to both derivates of LPS, that is, lipid A and tetra-acyl lipid A; thereby implying a higher and non-selective sensitivity of the murine TLR4 system towards its ligands | In humans, TLR4 confers a response to only the intact lipid A molecule, which implies a relative selectivity of human TLR4 system towards its ligands | 2, 65, 124 |
| P2X7 receptor | The Purinergic receptors system is crucial for the vaccination and chemotherapeutic response to ICD; effect characterized in P2rx7 KO-mice | Purinergic receptor antagonist, NF279, is not able to effectively block the murine P2X7 receptor-mediated calcium influx | Purinergic receptor antagonist, NF279, effectively blocks human P2X7 receptor-mediated calcium influx | 2, 65, 125 |
| Perforin | The perforins, which are essential for the cytotoxic NK/CTL cell functions; crucial for the vaccination and chemotherapeutic response to ICD; effect characterized in Prf1 KO-mice | — | — | 2 |
| TNF and TNF receptor | The TNF signalling system is essential for the vaccination response to ICD; effect characterized in Tnfa and Tnfr KO-mice | TNF is capable of activating the P-selectin promoter. P-selectins are important for leukocyte rolling | The P-selectin promoter is unresponsive to inflammation | 2, 65, 126 |
Abbreviations: CTL, cytotoxic T lymphocytes; CXCL, CXC ligand; CXCR, CXC chemokine receptor; ICD, immunogenic cell death; IFN, interferon; IL, interleukin; KO, knock-out; LPS, lipopolysaccharide; NK, natural killer; NLRP3, NACHT, LRR and PYD domains-containing protein 3; PBMC, peripheral blood mononuclear cells; TGF, transforming growth factor; Th, T helper; TLR, Toll-like receptor; TNF, tumour necrosis factor