TNFRSF18 Specific Neutra™ Antibody Products
Product listTumor necrosis factor receptor superfamily member 18 (TNFRSF18) is also named CD357 and GITR. TNFRSF18 has two isoforms. The isoform 1 is expressed on the cell membrane as a single-pass type I membrane protein, while isoform 2 is secreted outside the cell. TNFRSF18 is overexpressed in normal tissues such as the cervix, skin, whole blood, and saliva. Foxp3+CD4+ regulatory T cells (Treg) and activated CD4+ and CD8+ T cells consistently express high levels of TNFRSF18. As a receptor for TNFSF18, TNFRSF18 is involved in the regulation of T-cell immune effects.
Its Gene ID is 8784, OMIM ID is 603905, and UniProtKB ID is Q9Y5U5.
Function of TNFRSF18 Signalling Pathways
TNFRSF18 (GITR) and its ligand GITRL play important roles in modulating various types of immune cells in many immunological conditions. Here are some functions in which TNFRSF18 may be involved.
- Expression of TNFRSF18 on Treg cells resists suppression of Treg cells and enhances their proliferation in mice.
- TNFRSF18 stimulates cytokine production, apoptosis, and ICAM-1 regulation in primary macrophages.
- Expression of TNFRSF18 on effector T cells promotes proliferation, cytotoxicity, and cytokine production and inhibits apoptosis.
- Expression of GITRL on tumor cells enhances anti-tumor immune functions via the production of proinflammatory cytokines.
Fig.1 Effects of TNFRSF18 (GITR) signal pathways on the indicated cells.1
Immunotherapy Strategy of TNFRSF18
In the tumor microenvironment, activated Treg cells express the highest level of TNFRSF18, and multimerization of TNFRSF18 can lead to a variety of costimulatory immune functions, such as increasing immune cell proliferation and cytokine production.
The combination of reduced immunosuppression by Treg depletion and enhanced costimulatory function of CD8+ Teff cells leads to improved antitumor immunity.
- Biased depletion of Treg cells by binding TNFRSF18 on Treg cells with anti-TNFRSF18 antibodies that also bind to activating FcγR on NK cells (or macrophages).
- Oligomerization of TNFRSF18 on Teff cells by treatment with multivalent GITRL.
- FcR-mediated cross-linking by agonistic anti-TNFRSF18 antibodies with activating FcγR+ immune cells.
Fig. 2 The functions of TNFRSF18 (GITR) modulation in antitumor immunity.2
References
- Placke, Theresa.; et al. "Glucocorticoid-induced TNFR-related (GITR) protein and its ligand in antitumor immunity: functional role and therapeutic modulation." Journal of Immunology Research 2010 (2010).
- Knee, Deborah.; et al. "Rationale for anti-GITR cancer immunotherapy." European journal of cancer 67 (2016): 1-10.
