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The IL-8/IL-8R Axis: A Double Agent in Tumor Immune Resistance

Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Author to whom correspondence should be addressed.
Academic Editor: Theresa L. Whiteside
Vaccines 2016, 4(3), 22;
Received: 11 April 2016 / Revised: 31 May 2016 / Accepted: 21 June 2016 / Published: 24 June 2016
(This article belongs to the Special Issue Mechanisms of Tumor Escape from Host Immunity)
Interleukin-8 (IL-8, CXCL8) is a pro-inflammatory chemokine produced by various cell types to recruit leukocytes to sites of infection or tissue injury. Acquisition of IL-8 and/or its receptors CXCR1 and CXCR2 are known to be a relatively common occurrence during tumor progression. Emerging research now indicates that paracrine signaling by tumor-derived IL-8 promotes the trafficking of neutrophils and myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment, which have the ability to dampen anti-tumor immune responses. Furthermore, recent studies have also shown that IL-8 produced by the tumor mass can induce tumor cells to undergo the transdifferentiation process epithelial-to-mesenchymal transition (EMT) in which tumor cells shed their epithelial characteristics and acquire mesenchymal characteristics. EMT can increase metastatic dissemination, stemness, and intrinsic resistance, including to killing by cytotoxic immune cells. This review highlights the dual potential roles that the inflammatory cytokine IL-8 plays in promoting tumor resistance by enhancing the immunosuppressive microenvironment and activating EMT, and then discusses the potential for targeting the IL-8/IL-8 receptor axis to combat these various resistance mechanisms. View Full-Text
Keywords: IL-8; CXCR1/2; EMT; neutrophil; MDSC; brachyury; immune resistance IL-8; CXCR1/2; EMT; neutrophil; MDSC; brachyury; immune resistance
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David, J.M.; Dominguez, C.; Hamilton, D.H.; Palena, C. The IL-8/IL-8R Axis: A Double Agent in Tumor Immune Resistance. Vaccines 2016, 4, 22.

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