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Cancer Immunology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Osama Al Hamarneh, John Greenman
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].
Cell-Biomaterial constructs for wound healing and skin regeneration
Published in Drug Metabolism Reviews, 2022
Ingrid Safina, Luke T. Childress, Srinivas R. Myneni, Kieng Bao Vang, Alexandru S. Biris
Brant et al. compared the gene expression profile in full-thickness excisional wounds at different days post-wounding between two mice models, Acomys (known to go through scarless wound healing) (Seifert et al. 2012) and Mus (go through scarring wound healing) (Brant et al. 2015). 84 genes involved in different phases of wound healing were studied, with emphasis given to those involved in inflammatory response and ECM remodeling. The researchers found that for the c-x-c motif family of inflammatory chemokines, whose function is to attract immune cells at the wound site, Cxcl1, Cxcl3, and Cxcl5 were significantly upregulated (two to three-fold increase) in Mus at days 3 and 5 post-wound compared to normal skin. In contrast, in Acomys, there was zero to a non-significant amount of transcripts Cxcl1 and Cxcl5. On the other hand, Tgf-β1—known to be involved in almost all phases of wound healing—was upregulated nearly three-fold in Mus and seven-fold in Acomys compared to normal skin. Based on the previous notion that high levels of Tgf-β1 contribute significantly to scarred wound healing, it is intriguing to find high levels of Tgf-β1 present in Acomys wound healing, given that Acomys wounds heal in a scarless manner. A complete list of genes expressed in scarless versus scarring wound healing between Acomys and Mus mouse models can be found in the referenced study (Brant et al. 2015).
Dysregulation of tumour microenvironment driven by circ-TPGS2/miR-7/TRAF6/NF-κB axis facilitates breast cancer cell motility
Published in Autoimmunity, 2021
Shengting Wang, Xinghua Feng, Yufang Wang, Qian Li, Xiaoming Li
Given that TME remodelling is critical for cancer cell motility, we then designed an in vitro model for testing the relationship between circ-TPGS2-related TME and BC cell migration (Figure 3(A)). Transwell assay showed that the migratory ability of MCF-7 cells was significantly enhanced after treatment with circ-TPGS2-overexpressed condition medium (Figure 3(B)). Then, we tested the levels of some chemokines, the results showed that chemokines for neutrophils including CXCL1, CXCL3, CXCL8 and CXCL20 were increased in circ-TPGS2-overexpressed MCF-7 cells as compared to control cells (Figure 3(C)). And knockdown of circ-TPGS2 led to an opposite result (Figure 3(D)). Importantly, circTPGS2-overexpressed condition medium endowed greater expression change of these four chemokines (Figure 3(E)). Moreover, we designed an in vitro chemotaxis model to assess the intercellular effect of circ-TPGS2 in TME remodelling (Figure 3(F)). The results showed that the supernatant of circ-TPGS2-overexpressed MCF-7 cells recruited more leukocytes than that of control MCF-7 cells (Figure 3(G)), and most of them were CD15+ neutrophils (Figure 3(H)). And above effect was disappeared after synchronously knockdown of circ-TPGS2 (Figure 3(G, H)). These results suggest that circ-TPGS2 forms a unique TME enriched with neutrophils via autocrine and paracrine manners in BC.