Tumor Necrosis Factor-α (TNF-α)

Short Introduction to TNF-α

TNF-α is a multifunctional cytokine that is involved in a variety of immune responses such as apoptosis, cell survival, inflammation by two distinct receptors (TNFR-1 and TNFR-2). The major signaling pathway of TNFR-associated factor 2 (TRAF-2) is the activation of nuclear factor kappa B (NF-κB) via NF-κB-inducing kinase and inhibitor of nuclear factor kappa-B kinase (IKK) complex.

TNF-α and γδ T Cell

Human Vδ2 T cells have an important function in host defense. However, they have different Ag recognition and immunoregulation mechanisms distinct from conventional T cells.

TNF-α plays a critical role in regulating human Vγ2Vδ2 T cell immune responses. When TNF-α or its receptor was blocked, the Vδ2 T cell responses to antigen (Ag) stimulation, including activation, proliferation, cytokine production, and tumor cell cytotoxicity, were impaired significantly.

Scientists examined the peripheral Vδ2 T cells from patients with Rheumatoid Arthritis (RA) treated with etanercept, a kind of TNF-α receptor fusion protein. Results showed that the percentage of Vδ2 T cells could be restored in patients with RA after treatment with etanercept. TNF-α antagonist treatment down-regulated the expression of CCR5 and CXCR3 on Vδ2 T cells in patients with RA.

TNF-α and Tumor

The secretion of TNF-α by γδ T cells is promoted by numerous stimuli, including TCR agonists, ligands of NKG2D, and certain cytokines, such as Interleukin 12 (IL-12) and Interleukin 18 (IL-18). TNF-α inhibits cancer growth through several mechanisms, including the enhancement of antitumor immunity, and the inhibition of cancer angiogenesis.

A fusion protein coupling TNF to the Cys-Asn-Gly-Arg-Cys peptide can target the aminopeptidase N expressed by tumor blood vessels, and prove to be more efficient than TNF alone at reducing tumor growth in murine melanoma and lymphoma models.

Fig.1 Role of TNF in cancer-associated immune responses. (Bruno, 2019)

Not only can TNF inhibit anti-tumor immune responses via direct modulation of the activation, function, and survival of leukocytes during cancer progression, but it can also alter the phenotype of cancer cells so that they become less visible to T cells, and express immune inhibitory molecules.

Creative Biolabs is a well-executed partner in the biological field that has won a high reputation worldwide for successfully achieving numerous challenging programs. If you are interested in TNF-α and other cytokines secreted by γδ T cells, please contact us.

Reference

1. Bruno, Ségui.; et al. The TNF Paradox in Cancer Progression and Immunotherapy. Frontiers in Immunology. 2019, 10.