Cancer Immunology
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Immune suppressive cytokines, whether produced by tumour cells or by stromal cells, seem to control the cross-talk between cells within the TME during tumour progression (Figure 16.1). Furthermore the release of such cytokines induces ECM remodelling, basement membrane degradation, tumour cell proliferation and angiogenesis, and hence favours tumour progression and metastasis. In studies on HNSCC cell lines, fibroblasts and stromal endothelial cells have been shown to express a suppressive cytokine/chemokine milieu when co-cultured with HNSCC cells.39 CAF showed an increase in the expression of a number of pro-inflammatory cytokines and chemokines including CCL7, CXCL1, CXCL2, CXCL3 and CXCL8 when compared with CAF cultured alone.40 Similarly, type I collagen was found to markedly stimulate immune-suppressive cytokine expression such as IL-1α, IL-1β, IL-6, TNF-α, TGF-β and MMP-2 in metastatic HNSCC cell lines compared with that of the primary cancer cell lines.41
Circulating biomarkers of response to immunotherapy and immune-related adverse events
Published in Expert Review of Molecular Diagnostics, 2022
Zachary Garrison, Noah Hornick, Jeffrey Cheng, Rajan P. Kulkarni
CXCL5 is a member of a family of angiogenic chemokines that include CXCL1, CXCL2, CXCL3, CXCL6, CXCL7, and CXCL8. It has long been studied for its role in inflammation and cancer development [80]. More recently, CXCL5 has been identified as a biomarker of TH-17 cell-mediated autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and pemphigus vulgaris [81–83]. This influence on inflammation has also been observed to extend to immune therapy-induced irAEs. A study of advanced melanoma patients on nivolumab identified changes to CXCL5 levels for several types of inflammatory related irAEs including hypophisitis, thyroid dysfunction, adrenal insufficiency, psoriasiform dermatitis, interstitial pneumonia, hepatitis, radiation dermatitis, rheumarthritis, biliary tract disorder, and bursitis, though they did not find a significant trend in their limited sample size [84]. This relationship was also correlated with serum levels of CD163 expressing macrophages. CD163, a receptor found on monocytes [85,86], is linked to CXCL5 via their shared presence on tumor associated macrophages (TAMs). TAM production of CXCL5 [87] is the most rational explanation for the parallel correlation of CXCL5/CD163 and irAEs. CD163+ macrophages are a key component of tumor infiltrating immune cells that produce chemokines associated with cancer development and inflammation [88]. They have already been identified as a marker of autoimmune diseases such as rheumatoid arthritis, pemphigus vulgaris, and bullous pemphigoid [85].
Discovery and characterization of a neutralizing pan-ELR+CXC chemokine monoclonal antibody
Published in mAbs, 2020
Jeffrey S. Boyles, Catherine B. Beidler, Beth A. Strifler, Daniel S. Girard, Zhanna Druzina, Jim D. Durbin, Michelle L. Swearingen, Linda N. Lee, Kristine Kikly, Sudhakar Chintharlapalli, Derrick R. Witcher
The CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2) are G-protein coupled receptors (GPCR) expressed on granulocytes, monocytes, mast cells, and some natural killer cells that are capable of activating multiple downstream signaling pathways.1,2 Chemokines have been classified into 4 subfamilies, based on the presence of cysteines at the amino terminal: CXC, CC, CX3C and C.3,4 Among chemokine subfamilies, CXC chemokines can be further subclassified into Glu-Leu-Arg (ELR+) and ELR− CXC chemokines based on the presence or absence of a tripeptide ELR motif at the amine terminus. The ligands for CXCR1 and CXCR2 make up the ELR+CXC chemokine family. Despite the conserved structure and shared receptors, these chemokines share very little sequence homology outside of the ELRCXC motif (Figure 1). In humans, CXCL6 and CXCL8 signal through CXCR1, while all seven chemokines (CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8) signal through CXCR2.5 Chemokine affinities to the receptors are in the single-digit nM range, and they typically have short turnover rates as they rapidly bind receptor, internalize, and are degraded.6,7 Characteristic of ELR+CXC chemokines is their ability to specifically recruit neutrophils into inflamed tissues.
IL-17 induces antitumor immunity by promoting beneficial neutrophil recruitment and activation in esophageal squamous cell carcinoma
Published in OncoImmunology, 2018
Chang-Long Chen, Ying Wang, Chun-Yu Huang, Zi-Qi Zhou, Jing-Jing Zhao, Xiao-Fei Zhang, Qiu-Zhong Pan, Jiang-Xue Wu, De-Sheng Weng, Yan Tang, Qian Zhu, Lu-Ping Yuan, Jian-Chuan Xia
Our findings are supported by many other studies showing that IL-17 could recruit neutrophils by increasing epithelial cell or tumor cell-derived CXC chemokines including CXCL2 and CXCL3.16,35 Although the mechanism underlying the promotion of IL-17 on CXCL2 and CXCL3 production is unclear, extensive studies have demonstrated that IL-17 exerts its effects on the expression of chemokines through NF-κB and MAPKs signaling pathways.36,37 To explore whether IL-17 enhances CXCL2 and CXCL3 expression via NF-κB or MAPKs signaling pathways, we used specific siRNA to inhibit NF-κB (NF-κB1) or MAPK (p38) expression in the ESCC tumor cells (EC109 and KYSE30).However, we found that inhibition of NF-κB1 or p38 did not affect the increase of CXCL2 and CXCL3 production by IL-17 in EC109 and KYSE30 cells (data not shown). These indicates that other mechanism should be investigated underlying the impact of IL-7 on chemokines expression in ESCC.
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