Myeloid‐derived suppressor cells as effectors of immune suppression in cancer

Pyzer, Athalia R.; Cole, Leandra; Rosenblatt, Jacalyn; Avigan, David

doi:10.1002/ijc.30232

Cited by 87 publications

(64 citation statements)

References 214 publications

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“…There is increasing evidence for the crosstalk between MDSCs and cancer cells as a new fuel for the cancer deteriorative machinery. [25,32,33] However, the nonimmunological effects of MDSCs are poorly studied in human CRC. [25,32,33] However, the nonimmunological effects of MDSCs are poorly studied in human CRC.…”

Section: Discussionmentioning

confidence: 99%

Granulocytic Myeloid‐Derived Suppressor Cells Promote the Stemness of Colorectal Cancer Cells through Exosomal S100A9

et al. 2019

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Cancer stem cells play a critical role in colorectal cancer (CRC) progression. Myeloid‐derived suppressor cells (MDSCs) promote tumor progression through multiple mechanisms in CRC. The roles of MDSCs in CRC cell stemness are unclear. MDSC‐derived exosomes are proposed to act as intercellular messengers. Herein, it is reported that granulocytic MDSCs (G‐MDSCs) promote CRC cell stemness and progression in mice through exosomes. It is found that S100A9, is highly expressed in G‐MDSC‐derived exosomes, and its blockade suppresses CRC cell stemness and the susceptibility of mice to AOM/DSS‐induced colitis‐associated colon cancer. Hypoxia induces G‐MDSCs to secrete more exosomes in a hypoxia‐inducible factor 1α (HIF‐1α)‐dependent manner, and respiratory hyperoxia can reduce CRC cells stemness through the inhibition of GM‐Exo production. Study‐based CRC patients also show that human MDSCs enhance CRC cell stemness and growth via exosomal S100A9, and plasma exosomal S100A9 level in CRC patients is markedly higher than that in healthy subjects. Thus, this study suggests that G‐MDSCs promote CRC cell stemness and growth through exosomal S100A9. Moreover, respiratory hyperoxia may be a beneficial strategy to reduce CRC cells stemness through the inhibition of GM‐Exo production. MDSCs exosomal S100A9 may be a marker for predicting the development of CRC.

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Section: Discussionmentioning

confidence: 99%

Granulocytic Myeloid‐Derived Suppressor Cells Promote the Stemness of Colorectal Cancer Cells through Exosomal S100A9

et al. 2019

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“…Released exosomes along with secretions rich in factors of the VEGF family, including the PGF, trigger activation and recruitment of vascular endothelial growth factor receptor 1-expressing myeloid cells that will locally develop favorable places for metastatic colonizing (53). Trophoblast as well as cancer cells interact with the host organism to promote the recruitment of myeloid-derived suppressor cells that are effectors of immune tolerance (54, 55). …”

Section: Trophoblastic-like Transdifferentiationmentioning

confidence: 99%

Hypothesis about Transdifferentiation As Backbone of Malignancy

Piechowski¹

2017

Front. Oncol.

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Background: Cancer is mainly watched through the prism of random mutations and related corruption of signaling pathways. However, it would seem puzzling to explain the tumor organization, pugnacity and steady evolution of the tumorous disease and, moreover, a systematic ascendancy over the healthy tissues, only through stochastic genomic alterations.Malignancy specific properties: Considering the core characteristics of cancer cells, it appears that two major sets of properties are emerging, corresponding to wellidentified physiological phenotypes, i.e., (1) the trophoblastic logistical functions for cell survival, protection, expansion, migration, and host-tissue conditioning for angiogenesis and immune tolerance and (2) the sexual functions for genome maintenance. To explain the resurgence of these trophoblastic and sexual phenotypes, a particular cell reprogramming, to be called "malignant transdifferentiation" in view of its key role in the precancer-to-cancer shift, appears to be a convincing hypothesis.perspectives: The concept of malignant transdifferentiation, in addition to oncogenic mutations, would determine a more rational approach of oncogenesis and would open so far unexplored ways of therapeutic actions. Indeed, the trophoblastic phenotype would be a good candidate for therapeutic purposes because, on the one hand, it covers numerous properties that all are vital for the tumor, and on the other hand, it can be targeted with potentially no risk of affecting the healthy tissues as it is not expressed there after birth.

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“…Accumulating evidence suggests that the high infiltration of immature myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs), fosters potent immunosuppressive tumor microenvironment activity by dampening T-cell activation. 13 MDSCs and TAMs also promote tumor progression by regulating the survival, angiogenesis, and metastases of tumor cells.…”

mentioning

confidence: 99%

Inhibition of SRC family kinases reduces myeloid‐derived suppressor cells in head and neck cancer

Mao

Deng

et al. 2016

Intl Journal of Cancer

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SRC family kinases (SFKs), a group of nonreceptor tyrosine kinases, modulate multiple cellular functions, such as cell proliferation, differentiation and metabolism. SFKs display aberrant activity in progressive stages of human cancers. However, the precise role of SFKs in the head and neck squamous cell carcinoma (HNSCC) signaling network is far from clear. In this study, we found that the inhibition of SFKs activity by dasatinib effectively reduced the tumor size and population of MDSCs in the HNSCC mouse model. Molecular analysis indicates that phosphorylation of LYN, rather than SRC, was inhibited by dasatinib treatment. Next, we analyzed LYN expression by immunostaining and found that it was overexpressed in the human HNSCC specimens. Moreover, LYN expression in stromal cells positively correlated with myeloid-derived suppressor cells (MDSCs) makers CD11b and CD33 in human HNSCC. The dual positive expression of LYN in epithelial and stromal cells (EPI 1 SRT 1 )was associated with unfavorable overall survival of HNSCC patients. These findings indicate that SFKs may be a potential target for an effective immunotherapy of HNSCC by decreasing MDSCs and moreover, LYN will have an impact on such therapeutic strategy.

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Myeloid‐derived suppressor cells as effectors of immune suppression in cancer

Cited by 87 publications

References 214 publications

Granulocytic Myeloid‐Derived Suppressor Cells Promote the Stemness of Colorectal Cancer Cells through Exosomal S100A9

Granulocytic Myeloid‐Derived Suppressor Cells Promote the Stemness of Colorectal Cancer Cells through Exosomal S100A9

Hypothesis about Transdifferentiation As Backbone of Malignancy

Inhibition of SRC family kinases reduces myeloid‐derived suppressor cells in head and neck cancer

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