Lymphotoxin-alpha (LT-α) formerly known as tumor necrosis factor-beta (TNF-β)[5][6] is a protein that in humans is encoded by the LTAgene.[7][8] Belonging to the hematopoietic cell line, LT-α exhibits anti-proliferative activity and causes the cellular destruction of tumor cell lines.[7] As a cytotoxic protein, LT-α performs a variety of important roles in immune regulation depending on the form that it is secreted as. Unlike other members of the TNF superfamily, LT-α is only found as a soluble homotrimer, when found at the cell surface it is found only as a heterotrimer with LTβ.[9]
LT-α has a significant impact on the maintenance of the immune system including the development of secondary lymphoid organs.[10][11] Absence of LT-α leads to the disruption of gastrointestinal development, prevents Peyer's patch development, and results in a disorganized spleen.[12]
As a signaling molecule, LT-α is involved in the regulation of cell survival, proliferation, differentiation, and apoptosis.[13] LT-α plays an important role in innate immune regulation and its presence has been shown to prevent tumor growth and destroy cancerous cell lines.[14] In contrast, unregulated expression of LT-α can result in a constantly active signaling pathway, thus leading to uncontrolled cellular growth and creation of tumors.[13] Hence depending on the context, LT-α may function to prevent growth of cancer cells or facilitate the development of tumors. Furthermore, LT-α effects depend on the type of organ it acts upon, type of cancer cells, cellular environment, gender, and time of effect during an immune response.[15][14]
^Calmon-Hamaty F, Combe B, Hahne M, Morel J. Lymphotoxin α revisited: general features and implications in rheumatoid arthritis. Arthritis Res Ther. 2011 Jul 26;13(4):232. doi: 10.1186/ar3376. PMID 21861866; PMCID: PMC3239340.
^Aggarwal BB, Eessalu TE, Hass PE (February 1986). "Characterization of receptors for human tumour necrosis factor and their regulation by gamma-interferon". Nature. 318 (6047): 665–7. doi:10.1038/318665a0. PMID3001529. S2CID4341571.