Regulation of the anti-tumour immune response by cancer-associated fibroblasts

Harper, J. A.; Sainson, Richard C.A.

doi:10.1016/j.semcancer.2013.12.005

Cited by 225 publications

(207 citation statements)

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“…Moreover, they modulate the inflammatory response in tumor tissues. CAF can express interleukin (IL)-6, IL-1␤, and TNF␣ and chemokines, such as CXCL1, -2, -12, and -14 and CCL2, -5, and -7 (1,4,5). They are involved in the recruitment of immune cells, such as macrophages, myeloid-derived suppressor cells, and T lymphocyte subsets, which may in turn show tumor-promoting properties (1).…”

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confidence: 99%

Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts

Kretschmer

Freudenberger

Twarock

et al. 2016

Journal of Biological Chemistry

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The aim of this study was to characterize the interaction of KYSE-410, an esophageal squamous cell carcinoma cell line, and fibroblasts with respect to the extracellular matrix component hyaluronan (HA) and chemokine expression. KYSE-410 cells induced the mRNA expression of HA synthase 2 (Has2) in normal skin fibroblasts (SF) only in direct co-cultures. Parallel to Has2 mRNA, Has2 antisense RNA (Has2os2) was up-regulated in co-cultures. Knockdown of LEF1, a downstream target of Wnt signaling, abrogated Has2 and Has2os2 induction. After knockdown of Has2 in SF, significantly less ␣-smooth muscle actin expression was detected in co-cultures. Moreover, it was investigated whether the phenotype of KYSE-410 was affected in co-culture with SF and whether Has2 knockdown in SF had an impact on KYSE-410 cells in co-culture. However, no effects on epithelial-mesenchymal transition markers, proliferation, and migration were detected. In addition to Has2 mRNA, the chemokine CCL5 was up-regulated and CCL11 was down-regulated in SF in co-culture. Furthermore, co-cultures of KYSE-410 cells and cancer-associated fibroblasts (CAF) were investigated. Similar to SF, Has2 and Ccl5 were up-regulated and Ccl11 was down-regulated in CAF in co-culture. Importantly and in contrast to SF, inhibiting HA synthesis by 4-methylumbelliferone abrogated the effect of co-culture on Ccl5 in CAF. Moreover, HA was found to promote adhesion of CD4 ؉ but not CD8 ؉ cells to xenogaft tumor tissues. In conclusion, direct co-culture of esophageal squamous cell carcinoma and fibroblasts induced stromal HA synthesis via Wnt/LEF1 and altered the chemokine profile of stromal fibroblasts, which in turn may affect the tumor immune response.

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confidence: 99%

Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts

Kretschmer

Freudenberger

Twarock

et al. 2016

Journal of Biological Chemistry

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“…The interactions among these cell types contribute to tumor development and progression. Tumor-associated macrophages and cancer-associated fibroblasts regulate tumor metabolism and engender an immune-suppressive environment by secreting TGF-β and other cytokines (21). Fluctuations in energy sources and oxygen within a tumor contribute to malignant progression and cell phenotypic diversity (22,23).…”

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confidence: 99%

Modeling putative therapeutic implications of exosome exchange between tumor and immune cells

Huang

Hanash

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Development of effective strategies to mobilize the immune system as a therapeutic modality in cancer necessitates a better understanding of the contribution of the tumor microenvironment to the complex interplay between cancer cells and the immune response. Recently, effort has been directed at unraveling the functional role of exosomes and their cargo of messengers in this interplay. Exosomes are small vesicles (30-200 nm) that mediate local and long-range communication through the horizontal transfer of information, such as combinations of proteins, mRNAs and microRNAs. Here, we develop a tractable theoretical framework to study the putative role of exosome-mediated cell-cell communication in the cancer-immunity interplay. We reduce the complex interplay into a generic model whose three components are cancer cells, dendritic cells (consisting of precursor, immature, and mature types), and killer cells (consisting of cytotoxic T cells, helper T cells, effector B cells, and natural killer cells). The framework also incorporates the effects of exosome exchange on enhancement/reduction of cell maturation, proliferation, apoptosis, immune recognition, and activation/ inhibition. We reveal tristability-

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“…As such, CAFs can potentially affect both innate and adaptive antitumor immune response [8,9]. For example, the secretion of CXCL12/SDF1 and CCL2/MCP-1 by CAFs is potentially involved in macrophages attraction in the tumor microenvironment and in their differentiation into a M2 immunosuppressive phenotype [10].…”

Section: Descriptionmentioning

confidence: 99%