Targeting myeloid cells in the tumor sustaining microenvironment

Schupp, Jonathan; Krebs, Franziska; Zimmer, Niklas; Trzeciak, Emily R; Schuppan, Detlef; Tuettenberg, Andrea

doi:10.1016/j.cellimm.2017.10.013

Cited by 101 publications

(96 citation statements)

References 236 publications

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“…In contrast to C5aR2, we found that tumor-infiltrating leukocyte populations were altered in C5aR1-deficient mice, a result in accord with previous reports in other cancer models (7,8,10,12). The absence of C5aR1 signaling was associated with reduced percentages of tumor-infiltrating macrophages and T reg cells, both of which are known to suppress effective antitumor responses and promote tumor growth (47). We also found the proportion of Ly6C hi Ly6G 2 cells (Mo-MDSCs) reduced in tumors from C5aR1 2/2 mice.…”

Section: Discussionsupporting

confidence: 91%

C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma

et al. 2019

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The canonical complement component 5a (C5a) receptor (C5aR) 1 has well‐described roles in tumorigenesis but the contribution of the second receptor, C5aR2, is unclear. The present study demonstrates that B16.F0 melanoma cells express mRNA for both C5aR1 and C5aR2 and signal through ERK and p38 MAPKs in response to C5a. Despite this, C5a had no impact on melanoma cell proliferation or migration in vitro. In vivo studies demonstrated that the growth of B16.F0 melanoma tumors was increased in C5aR2–/– mice but reduced in C5aR1–/– mice and wild‐type mice treated with a C5aR1 antagonist. Analysis of tumor‐infiltrating leukocyte populations showed no significant differences between wild‐type and C5aR2–/– mice. Conversely, percentages of myeloid‐derived suppressor cells, macrophages, and regulatory T lymphocytes were lower in tumors from C5aR1–/– mice, whereas total (CD3+) T lymphocytes and CD4+ subsets were higher. Analysis of cytokine and chemokine levels also showed plasma IFN‐γ was higher and tumor C‐C motif chemokine ligand 2 was lower in the absence of C5aR1. The results suggest that C5aR1 signaling supports melanoma growth by promoting infiltration of immunosuppressive leukocyte populations into the tumor microenvironment, whereas C5aR2 has a more restricted but beneficial role in limiting tumor growth. Overall, these data support the potential of C5aR1‐inhibitory therapies for melanoma.—Nabizadeh, J. A., Manthey, H. D., Panagides, N., Steyn, F. J., Lee, J. D., Li, X. X., Akhir, F. N. M., Chen, W., Boyle, G. M., Taylor, S. M., Woodruff, T. M., Rolfe, B. E. C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma. FASEB J. 33, 11060–11071 (2019).http://www.fasebj.org

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Section: Discussionsupporting

confidence: 91%

C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma

et al. 2019

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“…Targeting of these cells during liver tumorigenesis represents a future challenge. The re‐education of myeloid cells in the tumor is currently considered a very promising approach . It consists in the reprogramming of inflammatory monocytes/macrophages to limit their pro‐tumoral potential.…”

Section: Discussionmentioning

confidence: 99%

Lect2 Controls Inflammatory Monocytes to Constrain the Growth and Progression of Hepatocellular Carcinoma

et al. 2019

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“…A large amount of research has confirmed that levels of TNF-α and IL-2 in the serum of patients with premature ovarian failure were significantly lower than those in unaffected group. Furthermore, the level of inflammatory factors decreased when the damaged ovarian function was repaired, indicating that inflammatory factors may be an important cause of premature ovarian failure [132][133][134][135]. Levels of inflammatory factors such as TNF-α, IL-1β, IL-2, IL-6, colony stimulating factor, zinc finger protein A20, heme oxygenase (HO-1) and many others are regulated by NF-κB.…”

Section: Immunosuppressive Mechanisms and Chronic Inflammationmentioning

confidence: 99%

Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

Zheng

Hong

et al. 2018

Cell Physiol Biochem

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The ovary is surrounded by a whitish layer of mesodermally derived ovarian surface epithelium (OSE) that lines the intraembryonic celom and comprises simple squamous to cuboidal to low pseudostratified columnar epithelial cells. Its integrity is maintained by simple desmosomes, incomplete tight junctions, several integrins and cadherins. Recent research has found that ovarian stem cells (OSCs) exist within the OSE and may be responsible for both neo-oogenesis and ovarian cancer during adult life. The factors determining whether OSCs undergo neo-oogenesis or ovarian cancer are of great interest to researchers and clinicians. Accumulating evidence suggests the mechanism for the decision of ovarian surface epithelial stem cells to undergo either neo-oogenesis or ovarian cancer transformation may comprise both internal and external factors. Here, we review recent progress on how the internal factors, including genes, signaling pathways and lncRNA: OSE stem cells mediate the development and progression of ovarian cancer through various genes such as p53, KRAS, BRAF, and PTEN, and mutations in PIK3CA, and through various signaling pathways, including TGF-B pathway, Wnt signaling pathway, Notch signaling pathway, NF-kB signal transducer and transcriptional activator 3 (STAT3) pathway and Hedghog (HH) pathway. A series of expressions of IncRNA have changed in epithelial ovarian cancer tissues and cell lines compared to normal ovarian tissues and cell lines. As well as external factors, including incessant ovulation, gonadotropin and chronicinflammation: Frequent ovulation, without long-term dormancy, increases the risk of illness, because repeated rupture and repair at the ovulation site provides an opportunity for the accumulation of genetic aberrations; FSH affects all aspects of ovarian cancer metastasis, such as inhibition of apoptosis, through Induction of increased expression of VEGFA (VEGF) to support tumor growth, promote vascular growth, and possibly alter certain oncogenic pathways, thereby promoting proliferation and invasive phenotypic inflammation contributes to tumorigenesis, which help determine whether OSCs undergo neo-oogenesis or ovarian tumorigenesis. Understanding this issue is critical for developing novel strategies for premature ovarian failure and ovarian cancer prevention and therapy.

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Targeting myeloid cells in the tumor sustaining microenvironment

Cited by 101 publications

References 236 publications

C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma

C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma

Lect2 Controls Inflammatory Monocytes to Constrain the Growth and Progression of Hepatocellular Carcinoma

Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

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