Leukemia inhibitory factor receptor complex (LIFR complex) (LIFR complex)

The Leukemia inhibitory factor receptor complex (LIFR complex) is a heterodimeric signaling unit composed of the Leukemia inhibitory factor receptor alpha subunit (LIFR; CD118) and the signal-transducing subunit glycoprotein 130 (gp130; CD130) (UniProt: P42702, P40189). On T cells and antigen-presenting cells (APCs), this complex acts as a critical switch in immune regulation, where LIF signaling promotes the induction of Foxp3+ regulatory T cells (Tregs) while suppressing the differentiation of pro-inflammatory Th17 cells (Metcalfe, 2011, PMID: 21844396). In the tumor microenvironment, the LIF/LIFR axis is frequently upregulated, contributing to immune evasion by recruiting myeloid-derived suppressor cells and inhibiting T cell activation, which correlates with poor clinical outcomes in cancers such as pancreatic adenocarcinoma and glioblastoma (Shi et al., 2019, PMID: 31142861). Therapeutic strategies targeting this complex include antagonistic monoclonal antibodies like MSC-1 (Azalentamab) to restore anti-tumor immunity and recombinant LIF (Emfilermin) or LIF-loaded nanoparticles to treat autoimmune disorders by enhancing immune tolerance (Metcalfe, 2020, PMID: 32508441). Due to the pleiotropic nature of LIF, safety considerations include monitoring for changes in bone metabolism and potential neurotrophic effects.

Other names

LIF receptor complexLIFR/gp130 complexCD118/CD130 complexLeukemia inhibitory factor receptor

The complex functions by binding the LIF ligand, which induces the heterodimerization of LIFR and gp130, subsequently activating the JAK/STAT3, PI3K/AKT, and MAPK signaling pathways to modulate immune cell phenotype and tumor cell stemness.