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IL-8
- Interleukin-8 (IL-8) is a cytokine produced by macrophages, monocytes, and
stromal cells 1
- IL-8 binds to G protein–coupled receptors chemokine (C-X-C motif) receptor 1 (CXCR1) and 2 (CXCR2) and promotes the recruitment of immunosuppressive MDSCs2,3
- During the normal healing process,
IL-8 also activates the angiogenic response to generate new blood vessels4
- Both tumor and tumor-associated stromal cells can upregulate production of IL-8, causing MDSCs to migrate to the tumor microenvironment where they suppress the antitumor immune response and expand the stroma2,4-7
- The stroma may act as a barrier to prevent immune recognition and subsequent
T-cell infiltration8,9 - In addition, tumor-derived IL-8 acts as a potent factor that promotes both angiogenesis and tumor metastasis4,10
- Elevated IL-8 levels are associated with poor prognoses in a wide range of tumor types11,12
- Preclinical studies suggest that blockade of IL-8 signaling reduces both the recruitment of CXCR1- and CXCR2-expressing MDSCs to the stromal barrier and tumor microenvironment, and angiogenesis2,10,13
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REFERENCES–IL-8
1. Duque GA, Descoteaux A. Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol. 2014;5:491. doi:10.3389/fimmu.2014.00491. 2. Alfaro C, Teijeira A, Oñate C, et al. Tumor-produced interleukin-8 attracts human myeloid-derived suppressor cells and elicits extrusion of neutrophil extracellular traps (NETs). Clin Cancer Res. 2016;22(15):3924-3936. 3. Waugh DJJ, Wilson C. The interleukin-8 pathway in cancer. Clin Cancer Res. 2008;14(21):6735-6741. 4. David JM, Dominguez C, Hamilton DH, Palena C. The