Table 2.
Molecules in immune tolerance in allergy and cancer.
| Section | Molecule | Function in allergy | In cancer |
|---|---|---|---|
| 4.1 | IgG4 antibodies | Induced in allergen immunotherapy; Function as blocking antibodies and via FcγRIIb |
Over-expressed in some malignancies Derived from intra-tumoural Bregs Correlate with progression |
| 4.2 | IgE and IgG repertoires | IgE: the major effector antibody in immediate type allergies, via high affinity binding to FcεRI; Responsible for antigen cross-presentation to T cells; IgE clones have increased persistence, more likely related to other switched isotypes, larger clonal families |
IgE and IgG: monoclonality in myelomas; Small sub-clones re-emerged at relapse alongside a dominant clone in B cell leukaemia |
| 4.3 | Free light chains (FLC) | Increased polyclonal FLC levels in allergies Activate mast cells |
Increased FCL: biomarker for poor prognosis in basal-like breast cancer |
| 4.4 | Regulatory cytokines and chemokines | IL-10 and TGF-β have pivotal role in tolerance establishment to allergens; CCL1:CCR8 axis plays a master role in immune regulation |
IL-10 and TGF-b derived from immune and cancer cells shape the immunosuppressive environment in cancer and correlate with disease progression; Controversial: the role of the CCL5:CCR5 axis; CCL3, -4, -5 derived from intratumoral myeloid derived suppressor cells (MDSCs) can recruit Tregs |
| 4.5 | Mast cell mediators and receptors | Secreted mediators and cytokines that support allergy and acute inflammation Interact with IgE and other isotypes |
Controversial; Can stimulate tumour growth (e.g. histamine, NGF, IL-8), neovascularization (e.g. VEGF, heparin, TGFβ), and suppress effector T cells, enhance Tregs via amphiregulin; On the contrary, can inhibit tumour growth, cause apoptosis (e.g. via TNFα, IFNγ, PAR-1/2), and attract leukocytes (e.g. IL-8, TNFα), inhibit metastasis via chondroitin sulphate |
| 4.6 | Lipocalins (LCN) | Sequester iron; LCN and iron levels decreased in allergy; Some allergens belong to the lipocalin family themselves |
LCN and iron levels are upregulated in cancer; form complexes with matrix-metallopeptidase 9 |