From: Eosinophils in the tumor microenvironment: implications for cancer immunotherapy
 | Name | Components | Function | ||
---|---|---|---|---|---|
Granule | Primary | CLC | Causes inflammation and stimulates Th2 cells, has lysophospholipase activity | ||
Secondary (specific, crystalloid, crystalline, alpha) | Crystalline core | MBP | Neutralizes heparin, is bactericidal by changing the negative charge of lipid bilayer and disorganizing it, toxic for helminths and airway epithelium, activates complement system, stimulates basophil/mast cell for histamine secretion | ||
GM-CSF | Eosinopoiesis induction | ||||
IL-4 | Th2 and M2 polarization, IgE class switching, CCL11 secretion | ||||
Cathepsin D, hydrolase, glucuronidase | ECM degradation | ||||
Matrix | ECP ribonuclease | • Forms toxic pores on target cell membranes and is bactericidal, antiviral, anti-helminth • Sends signals to other cells, degranulates mast cells | |||
EPX (EPO) | Cytotoxic, generates reactive oxygen species (ROS) for oxidative damage | ||||
EDN ribonuclease | Possesses antiviral activity | ||||
IL-2 | Crucial for the expansion of all T cells | ||||
IL-6 and APRIL | Support long-lived plasma cells and B cell development | ||||
IL-13 | Helps IL-4 with M2 polarization and IgE class switching | ||||
IL-10 | M2 polarization, immune cells’ suppression | ||||
IL-5, SCF | Eosinopoiesis, eosinophil activation, recruitment | ||||
IFN-γ | Th1 and M1 differentiation, CD8 + T cell stimulation, vessel normalization, antiviral, antibacterial, IL-12 production, tumor suppression | ||||
IL-12 | Th1 differentiation, IFN-γ production by NK cells and Th1 cells, Th2 inhibition | ||||
TNF, IL-1β | Have strong proinflammatory activities | ||||
TGF-α | Promotes epithelial wound healing and cell proliferation | ||||
TGF-β | • Plus IL-4: Th9 differentiation • Plus IL-2: Treg differentiation • plus IL-6/IL-21: Th17 differentiation Exacerbates tissue fibrosis IgA class swithcing | ||||
Histaminase | Degrades histamine | ||||
Collagenase, elastase, catalase, esterase | ECM degradation | ||||
NGF, PDGF, VEGF, EGF | Growth factors for proliferation of various cells | ||||
CCL7 (MCP-3) | A potent chemoattractant for monocytes, eosinophils, basophils, DCs, NK and T cells | ||||
CXCL1 (Groα) | Neutrophil chemoattractant, involved in angiogenesis and tumorigenesis | ||||
CCL11 (eotaxin-1) | The most important eosinophil chemoattractant, induces piecemeal degranulation (PMD) | ||||
CCL13 (MCP-4) | A major eosinophil, basophil, monocyte, T cell chemoattractant | ||||
CCL3 (MIP-1α) | Attracts macrophages, lymphocytes, and eosinophils | ||||
CCL5 (RANTES), CXCL9, CXCL10 (IP-10), CXCL16 | Secreted from activated eosinophil to recruit Th1, CD8 + T, and NK cells | ||||
CXCL12 (SDF-1) | A weak eosinophil chemoattractant | ||||
CCL17, CCL22 | Th2 recruitment to tissue, Treg recruitment (CCL22) | ||||
CCL20 (MIP-3α) | Induces eosinophil migration and activation | ||||
CCL9 (MIP-1γ) | Recruits DCs and macrophages to Peyer’s patches | ||||
Lipid bodies | LTC4, LTD4, LTE4 | Induce bronchoconstriction, mucus production, airway inflammation, eosinophil lineage commitment | |||
PGE1, PGE2 | Smooth muscle relaxant and vasodilator | ||||
TXB2 | Vasoconstriction and platelet aggregation | ||||
15-HETE | Vasoconstriction and angiogenesis promotion | ||||
PAF | Eosinophil chemoattractant, increases LTC4 production and eosinophil adhesion | ||||
COX, 5-lipoxygenase, LTC4 synthase | Esterify arachidonic acids and produce eicosanoids such as PGs and LTs | ||||
Receptors | Cytokine and growth factor receptors | IL-2Rα/β (CD25/CD122) | Binds to IL-2 that activates eosinophils to release EPX and induces chemotaxis | ||
IL-3Rα/β (CD123/CD131) | Binds to IL-3 that helps with eosinopoiesis | ||||
IL-4Rα/β (CD124/CD132) | Binds to IL-4 that activates eosinophils | ||||
IL-5Rα/β (CD125/CD131) | • IL-5Rα binds to IL-5 • IL-5Rβ transfers the signal | ||||
IL-9Rα/β (CD129/CD132) | Binds to IL-9 that promotes eosinophil, mast cell, Treg, Th17 growth | ||||
IL-13Rα1 (CD213a1) | Binds to IL-13 that promotes P-selectin expression on eosinophils | ||||
IFN-γR1 (CDw119) | Binds to IFN-γ which boosts eosinophil anti-tumor activity | ||||
TGF-βR1 | Binds to TGF-β | ||||
TNFαR1 and 2 (CD120a, b) | Bind to TNF-α that delays eosinophil apoptosis | ||||
IL-10Rb | Binds to IL-10 cytokine family such as IL-22 (important in antimicrobial peptide production) and IFN-λ (antiviral) | ||||
IL-13Rα1 (CD213a1) | Binds to IL-13 | ||||
IL-17 A/F R (IL-17RA/IL-17RC) | Bind to IL-17 A and IL-17F of Th17 to cause IL-1β and IL-6 production | ||||
IL-18R | Binds to IL-18 that increases LFA-1 and ICAM-1 expression | ||||
IL-23R (IL-23R/IL-12Rβ1) | Binds to IL-23 that increases IL-17RA expression and recruits eosinophils to lungs | ||||
IL-27R (gp130/WSX-1) | Binds to IL-27 that prolongs eosinophil survival by reducing apoptosis | ||||
IL-31R (IL-31RA/OSMRβ) | Binds to IL-31 that activates eosinophils | ||||
TSLPR | Binds to TSLP cytokine that modulates eosinophil survival and promotes eosinophilia | ||||
GM-CSFRα/β (CD116/CD131) | Binds to GM-CSF to help with eosinophil lineage commitment and survival | ||||
SCFR (KIT) (CD117) | Binds to SCF to help with eosinophil lineage commitment and survival | ||||
IL-25R and IL-33R (ST2) | Bind to IL-25 and IL-33 that modulate eosinophil survival and promote eosinophilia | ||||
Fc receptors | FcεRI | High-affinity IgE receptor that does not activate eosinophils | |||
FcεRII (CD23) | Low-affinity receptor for IgE | ||||
FcγRII (CD32) | Binds to IgG and triggers eosinophil activation | ||||
FcαRI (CD89) | Binds to IgA and triggers eosinophil activation and prevents apoptosis | ||||
FcγRI (CD64), FcγRIII (CD16) | Not constitutively expressed, upregulated by IFN-γ, C5a, PAF | ||||
Adhesion receptors | Integrin | CD11/CD18 (LFA1) | Binds to ICAM-1 (CD54) and -2 (CD102) for infiltration in airways | ||
CD11b/CD18 (CR3) | Binds to ICAM-1 and fibrinogen, binds to β−glucan to induce EDN release against fungi | ||||
CD11c/CD18 (CR4) | Binds to iC3b | ||||
CD49d/CD29 (VLA4) | Binds to VCAM-1 to carry out extravasation | ||||
Selectin | L-selectin (CD62L) | Binds to Sialyl Lewis X of GlyCAM-1, CD34, MadCAM-1 on endothelium for eosinophil tethering before integrin activation | |||
Others | PSGL-1 | Its Sialyl Lewis X (CD15s) binds to P-selectin (CD62P) and E-selectin (CD62E) on endothelium for eosinophil tethering before integrin activation | |||
Inhibitory receptors | Siglec-8 | Binds to sialic acid and induces eosinophil death | |||
Secretory proteins | VAMP-2, -7, -8, STX-17 | Located in granules and Sombrero vesicles, form SNARE complexes with STX-4 and SNAP-23, crucial for exocytosis and PMD | |||
Syntaxin-4 (STX-4), SNAP-23 | Located in plasma membrane, form SNARE complexes with VAMP-2, -7, -8, and STX-17, crucial for exocytosis and PMD | ||||
Pattern recognition receptors (PRRs) | TLR-1, -2, -4, -5, -6 | Present on cell surface and detect bacterial proteins, lipoproteins, and polysaccharides | |||
TLR-3, -7, -8, -9, -10 | Present in endosome and detect viral nucleic acids | ||||
CLRs | Detect fungal components | ||||
RLRs | Present in cytosol to detect viral dsRNA | ||||
RAGE | Binds to HMGB1 and promotes eosinophilia | ||||
NLRs | Present in cytosol and detect bacterial peptidoglycan | ||||
Chemokine receptors | CCR1 (CD191) | Binds to CCL3 (MIP1α), CCL5 (RANTES), CCL7 (MCP3), PAF | |||
CCR2 (CD192) | Binds to CCL7, CCL8 (MCP2) | ||||
CCR3 (CD193) | • Binds to eotaxins (CCL11, CCL24, CCL26) that greatly enhance eosinophil chemoattraction with IL-5 • Binds to CCL5 (RANTES), CCL13 (MCP4), CCL7, CCL8 | ||||
CCR4 (CD194) | Binds to CCL17 and CCL22 | ||||
CCR5 (CD195) | Binds to CCL1, CCL5, CCL7 | ||||
CCR6 (CD196) | Binds to CCL20 | ||||
CCR8 (CD198) | Binds to CCL1 that is bactericidal and recruits eosinophils | ||||
CCR9 (CD199) | Binds to CCL25 | ||||
CXCR2 (CD182) (IL-8Rβ) | Binds to CXCL1 | ||||
CXCR3 (CD183) | Binds to CXCL9, CXCL10 | ||||
CXCR4 (CD184) | Binds to CXCL12 | ||||
FPR1 | Binds to microbial peptides that induces leukocyte chemotaxis | ||||
Complement receptors | CR1 (CD35) | Binds to C3b, C4b, iC3b, C1q to activate eosinophils | |||
CR3 (CD11b/CD18) | Binds to iC3b and ICAM-1 | ||||
C3aR, C5aR, CR4, CD103 | Bind to complement components that activate and attract eosinophils | ||||
Eicosanoid receptors | CysLT1R, CysLT2R, LTB4R, PGD2R, PGE2R, PAFR, fMLPR | Bind to lipid mediators such as LTs and PGs | |||
MHC-II | Plus CD80/86 or CD40 | MHC-II presents T cells with antigen peptides and CD80/86 or CD40 provide co-stimulation | |||
HLA-DR | Upregulated in activated eosinophils |