The role of hypoxia in shaping the recruitment of proangiogenic and immunosuppressive cells in the tumor microenvironment

Chouaı̈b, Salem; Umansky, Viktor; Kiéda, Claudine

doi:10.5114/wo.2018.73874

Cited by 28 publications

(27 citation statements)

References 85 publications

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“…In the hypoxic TME, VEGF is thought to be the dominant chemoattractant for MDSCs, as it was shown that, both in mice and in non-small cell lung cancer (NSCLC) patients, hypoxia upregulates its expression and aids in MDSC accumulation [36]. This process of VEGF-mediated attraction to the TME is possible by means of VEGFR expression on MDSCs [37]. Primary tumor clusters can potentially gather MDSCs from the BM by releasing exosomes.…”

Section: Accumulation Of Mdscs To Tumor Sitesmentioning

confidence: 99%

“…The most common and well-studied mechanism of MDSC-mediated angiogenesis is the production of VEGF [36]. The VEGF family of proteins consists of VEGF-A, -B, and -C [37,58]. MDSCs exploit the abundance of VEGF in the TME, and via the tyrosine kinase receptor VEGFR, they are able to initiate a signaling cascade implicating JAK2/STAT3, resulting in the production of even more angiogenic molecules [59,60].…”

Section: The Vegf/vegfr Angiogenic Pathwaymentioning

confidence: 99%

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Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Vetsika

Koukos

Κotsakis

2019

Cells

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Myeloid-derived suppressor cells (MDSCs) constitute a vast population of immature myeloid cells implicated in various conditions. Most notably, their role in cancer is of great complexity. They exert immunosuppressive functions like hampering cancer immunity mediated by T lymphocytes and natural killer cells, while simultaneously they can recruit T regulatory cells to further promote immunosuppression, thus shielding tumor cells against the immune defenses. In addition, they were shown to support tumor invasion and metastasis by inducing vascularization. Yet again, in order to exert their angiogenic activities, they do have at their disposal a variety of occasionally overlapping mechanisms, mainly driven by VEGF/JAK/STAT signaling. In this concept, they have risen to be a rather attractive target for therapies, including depletion or maturation, so as to overcome cancer immunity and suppress angiogenic activity. Even though, many studies have been conducted to better understand these cells, there is much to be done yet. This article hopes to shed some light on the paradoxal complexity of these cells, while elucidating some of the key features of MDSCs in relation to immunosuppression and, most importantly, to the vascularization processes, along with current therapeutic options in cancer, in relation to MDSC depletion.

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Section: Accumulation Of Mdscs To Tumor Sitesmentioning

confidence: 99%

Section: The Vegf/vegfr Angiogenic Pathwaymentioning

confidence: 99%

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Vetsika

Koukos

Κotsakis

2019

Cells

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“…Hypoxia is a common phenomenon in the tumor microenvironment (47)(48)(49). Previous studies have revealed that tumor hypoxia alters the composition and activity of tumor-associated immune cells, and that numerous immune cells with immunosuppressive activities are recruited to tumor tissues to form the immunosuppressive microenvironment (18,50,51). Under hypoxic conditions, tumor cells and macrophages secrete a variety of cytokines and chemokines, including C-C motif chemokine (CCL)22, CCL28 and IL-10, which results in the recruitment of CD4 + CD25 + FOXP3 + Tregs from peripheral blood to inhibit T cell-mediated antitumor responses (18,52,53).…”

Section: Hypoxia-induced Recruitment Of Immunosuppressive Cells and Rmentioning

confidence: 99%

Role and mechanism of programmed death‑ligand�1 in hypoxia‑induced liver cancer immune escape (Review)

et al. 2020

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Immune escape plays a vital role in the development of liver cancer. The interaction between programmed death-ligand 1 (PD-L1) and programmed cell death-1 is a key mediator of cancer immune escape, which leads to the suppression of anticancer immunity and promotion of tumor progression. Hypoxia is a common phenomenon in the tumor microenvironment. Under hypoxic conditions, suppressive immune cells, such as regulatory T cells, myeloid-derived suppressor cells and M2 macrophages, are frequently recruited to tumor tissues to form the immunosuppressive microenvironment in liver cancer. These cells secrete cancer-promoting inflammatory cytokines, which activate the STAT3 and NF-κB signaling pathways. Recent studies have shown that STAT3 is associated with NF-κB and that these transcription factors are often co-activated to regulate tumor proliferation, survival, angiogenesis and invasion. The activation of STAT3 and NF-κB signaling pathways can directly and indirectly induce PD-L1 expression. Therefore, further understanding of the association between hypoxia and PD-L1 may help in the future treatment of liver cancer. The present review summarizes the recent progresses on PD-L1-mediated regulation and facilitation of liver cancer cell immune escape in response to hypoxia. Contents 1. Introduction 2. PD-L1/PD-1 interaction in the immune escape of liver cancer 3. Hypoxia-induced recruitment of immunosuppressive cells and regulation of PD-L1 expression 4. Involvement of STAT3 and NF-κB in the regulation of PD-L1 expression in liver cancer 5. Relevance for clinical practice 6. Conclusions

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“…The tumor microenvironment stimulates MDSCs also by other factors induced by local hypoxia and low pH ( 52 , 53 ). One of them is hypoxia-inducible factor (HIF).…”

Section: Myeloid-derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in Colorectal Cancer

Siemińska

Baran

2020

Front. Immunol.

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Colorectal cancer (CRC) remains one of the most common malignancies diagnosed worldwide. The pathogenesis of CRC is complex and involves, among others, accumulation of genetic predispositions and epigenetic factors, dietary habits, alterations in gut microbiota, and lack of physical activity. A growing body of evidence suggests that immune cells play different roles in CRC, comprising both pro-and anti-tumorigenic functions. Immunosuppression observed during cancer development and progression is a result of the orchestration of many cell types, including myeloid-derived suppressor cells (MDSCs). MDSCs, along with other cells, stimulate tumor growth, angiogenesis, and formation of metastases. This article focuses on MDSCs in relation to their role in the initiation and progression of CRC. Possible forms of immunotherapies targeting MDSCs in CRC are also discussed.

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The role of hypoxia in shaping the recruitment of proangiogenic and immunosuppressive cells in the tumor microenvironment

Cited by 28 publications

References 85 publications

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Role and mechanism of programmed death‑ligand�1 in hypoxia‑induced liver cancer immune escape (Review)

Myeloid-Derived Suppressor Cells in Colorectal Cancer

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