Lymphotoxin ?, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface

The unexpected role of lymphotoxin β receptor signaling in carcinogenesis: from lymphoid tissue formation to liver and prostate cancer development

“…Interestingly, murine and human TNFa and b genes are close to each other within the major histocompatibility complex region (mouse, chromosome 17 (Nedospasov et al, 1986a, b); man, short arm of chromosome 6 (Nedwin et al, 1985b;Muller et al, 1987)). Later a third ligand-homologous to TNFb-was identified within the major histocompatibility complex locus and named LTb (TNFSF3; (Hiserodt et al, 1977;Ware and Granger, 1979;Browning et al, 1993;Pokholok et al, 1995), whereas subsequently TNFb was termed LTa or TNFSF1B. At present, 19 different ligands belong to the TNFSF, including, for example, TRAIL, RANKL, BAFF, CD40 (Aggarwal, 2003), mediating their cellular response through 29 receptors, which contain an extracellular cysteine-rich domain (Aggarwal, 2003) and in some cases (for example, TNFR1, TNFR2, TRAIL R1, TRAIL R2, Fas) a death domain.…”

“…Although LTa mRNA expression is inducible in B-cells, LTb mRNA is constitutively produced (Browning et al, 1993;Worm and Geha, 1994). LTb is exclusively anchored in the membrane as a type II transmembrane protein, binding LTa to form membrane-anchored heterotrimers (LTa 1 b 2 and LTa 2 b 1 ; Browning et al, 1993Browning et al, , 1995. LTab heterotrimers can also be cleaved from the cell surface by matrix metalloproteases eliciting responses on distal cells (Young et al, 2010).…”

Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity

“…The immunologic importance of the cell-associated cytokines is largely unknown. On the other hand, IL-1, 23 TNF, 24 LT␣ 25 and IFN␥ 26 are expressed in two different versions, one is a membrane-bound form and the other is soluble form. While precise functional discrimination of the forms has not been made, the membrane-bound form of TNF has a unique function distinct from that of the soluble TNF.…”

“…Several cytokines are expressed as membrane-associated forms, soluble forms or proteolytically processed forms; IL-1, 23 TNF, 24 LT␣, 25 and IFN␥. 26 Genetically engineered membrane-bound forms can result in lower tox- icity of TNF and LT␣.…”

“…26 Genetically engineered membrane-bound forms can result in lower tox- icity of TNF and LT␣. 24,25 In some cases cytokines secreted by the tumor cells bind to receptors on the tumor cells and deliver effective signals by cell to cell contact. 27,28 In the present study, we have generated transfected tumor cells expressing a membrane-bound form of IL-4 (IL-4m).…”