C-X-C motif chemokine 9 (CXCL9)

C-X-C motif chemokine 9 (CXCL9), historically known as Monokine Induced by Gamma Interferon (MIG), is a small signaling protein and a potent chemoattractant for immune cells expressing the CXCR3 receptor, such as effector T cells and natural killer (NK) cells. It is primarily produced by macrophages, dendritic cells, and endothelial cells in response to interferon-gamma (IFNγ) stimulation via the JAK-STAT1 pathway. In the context of oncology, CXCL9 generally functions as a tumor suppressor by promoting the infiltration of cytotoxic lymphocytes and exerting angiostatic effects; consequently, high levels of CXCL9 are often predictive of a favorable response to immune checkpoint inhibitors like anti-PD-1 therapy. However, pathological overproduction of CXCL9 is a hallmark of hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH) and various autoimmune diseases, where it serves as a critical biomarker for monitoring systemic IFNγ activity. Therapeutic intervention typically involves suppressing CXCL9 production through IFNγ-targeted agents (e.g., emapalumab) or JAK inhibitors (e.g., ruxolitinib), while direct neutralizing antibodies are under investigation to mitigate inflammatory tissue damage.

Other names

Monokine induced by gamma interferonMIGHumigSCYB9Small-inducible cytokine B9CMKGamma-interferon-induced monokine

Neutralization of the CXCL9 ligand to prevent recruitment of CXCR3-expressing immune cells or inhibition of the upstream IFN-gamma/JAK/STAT signaling pathway to suppress CXCL9 expression.