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Interleukin-27 subunit alpha (IL-27p28), also known as IL-30, is a component of the heterodimeric cytokine Interleukin-27, which also includes the EBI3 subunit (UniProt: Q8NEV9). IL-27 plays a dual role in the immune system, exhibiting both pro-inflammatory and anti-inflammatory properties by signaling through a receptor complex composed of IL-27Rα (WSX-1) and gp130 (PubMed: 12130629). It is particularly noted for its ability to promote Th1 cell differentiation while simultaneously suppressing Th17 responses and inducing the production of the anti-inflammatory cytokine IL-10 in T cells (PubMed: 28232553). In the context of oncology, IL-27 is often upregulated in the tumor microenvironment and can contribute to immune evasion by inducing the expression of inhibitory checkpoints like PD-L1 (PubMed: 33159057). Consequently, the p28 subunit has emerged as a therapeutic target, with monoclonal antibodies such as SRF388 (GS-4528) being developed to block its activity and enhance anti-tumor immunity (ClinicalTrials.gov: NCT04374877). Beyond cancer, IL-27 signaling is implicated in various autoimmune and infectious diseases, making it a versatile target for immunomodulation (PubMed: 24610874).
Monoclonal antibody-mediated inhibition of IL-27 signaling by binding to the p28 subunit
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