Myeloid-Derived Suppressor Cells in Human Cancer

Nagaraj, Srinivas; Gabrilovich, Dmitry I.

doi:10.1097/ppo.0b013e3181eb3358

Cited by 206 publications

(194 citation statements)

References 91 publications

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“…As previously described, the accumulation of MDSCs in animal models and human samples has been reported to be associated with defective dentritic cell function and inhibition of antigen-specific T-cell responses (15). To date, an increasing number of studies have been carried out to determine the phenotype of MDSC in murine models (16), however, limited studies are available to investigate the phenotype of MDSC in humans, particularly patients with breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of CD4+CD25+CD127− regulatory T cells and CD14+HLA−DR−/low myeloid-derived suppressor cells and their roles in the prognosis of breast cancer

Wang

Yang

2016

Biomedical Reports

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Section: Discussionmentioning

confidence: 99%

Identification of CD4+CD25+CD127− regulatory T cells and CD14+HLA−DR−/low myeloid-derived suppressor cells and their roles in the prognosis of breast cancer

Wang

Yang

2016

Biomedical Reports

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“…The characterization of human MDSCs deeply suffers from the lack of specific markers. Human MDSCs are generally identified as cells expressing the common myeloid marker CD33, lacking the expression of markers of mature myeloid and lymphoid cells, and able to suppress T cell activation [93,94]. The phenotype of human MDSCs seems to be dependent from the type of tumor born by the patient, suggesting that several cellular subsets may exist.…”

Section: Tamcs Functionsmentioning

confidence: 99%

Origin and Functions of Tumor-Associated Myeloid Cells (TAMCs)

Sica

Porta

Morlacchi

et al. 2011

Cancer Microenvironment

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The construction of an inflammatory microenvironment provides the fuel for cancer development and progression. Hence, solid tumors promote the expansion and the recruitment of leukocyte populations, among which tumor-associated myeloid cells (TAMCs) represent a paradigm for cancer-promoting inflammation. TAMCs group heterogeneous phagocytic populations stemming from a common myeloid progenitor (CMP), that orchestrate various aspects of cancer, including: diversion and skewing of adaptive responses; immunosuppression; cell growth; angiogenesis; matrix deposition and remodelling; construction of a metastatic niche and actual metastasis. Several evidence indicate that TAMCs show plasticity and/or functional heterogeneity, suggesting that tumour-derived factors promote their functional "reprogramming" towards protumoral activities. While recent studies have attempted to address the role of microenvironment signals, the interplay between cancer cells, innate and adaptive immunity is now emerging as a crucial step of the TAMCs reprogramming. Here we discuss the evidence for the differentiation of TAMCs during the course of tumor progression and the molecular mechanisms that regulate such event.

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“…24,25 Mouse MDSC consist of a heterogeneous population distinct from immature myeloid cells present in tumor-free mice. Two main MDSC subsets have been described: the monocytic subset (mMDSC, CD11b…”

Section: Gr1mentioning

confidence: 99%

Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade

et al. 2017

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Tumor angiogenesis promotes tumor growth and metastasis. Anti-angiogenic therapy in combination with chemotherapy is used for the treatment of metastatic cancers, including breast cancer but therapeutic benefits are limited. Mobilization and accumulation of myeloid-derived suppressor cells (MDSC) during tumor progression and therapy have been implicated in metastasis formation and resistance to antiangiogenic treatments. Here, we used the 4T1 orthotopic syngenic mouse model of mammary adenocarcinoma to investigate the effect of VEGF/VEGFR-2 axis inhibition on lung metastasis, MDSC and regulatory T cells (Tregs). We show that treatment with the anti-VEGFR-2 blocking antibody DC101 inhibits primary tumor growth, angiogenesis and lung metastasis. DC101 treatment had no effect on MDSC mobilization, but partially attenuated the inhibitory effect of mMDSC on T cell proliferation and decreased the frequency of Tregs in primary tumors and lung metastases. Strikingly, DC101 treatment induced the expression of the immune-suppressive molecule arginase I in mMDSC. Treatment with the arginase inhibitor N v -hydroxy-nor-Arginine (Nor-NOHA) reduced the inhibitory effect of MDSC on T cell proliferation and inhibited number and size of lung metastasis but had little or no additional effects in combination with DC101.In conclusion, DC101 treatment suppresses 4T1 tumor growth and metastasis, partially reverses the inhibitory effect of mMDSC on T cell proliferation, decreases Tregs in tumors and increases arginase I expression in mMDSC. Arginase inhibition suppresses lung metastasis independently of DC101 effects. These observations contribute to the further characterization of the immunomodulatory effect of anti-VEGF/VEGFR2 therapy and provide a rationale to pursue arginase inhibition as potential anti-metastatic therapy.

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Myeloid-Derived Suppressor Cells in Human Cancer

Cited by 206 publications

References 91 publications

Identification of CD4+CD25+CD127− regulatory T cells and CD14+HLA−DR−/low myeloid-derived suppressor cells and their roles in the prognosis of breast cancer

Identification of CD4+CD25+CD127− regulatory T cells and CD14+HLA−DR−/low myeloid-derived suppressor cells and their roles in the prognosis of breast cancer

Origin and Functions of Tumor-Associated Myeloid Cells (TAMCs)

Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade

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