Identification of a New Subset of Myeloid Suppressor Cells in Peripheral Blood of Melanoma Patients With Modulation by a Granulocyte-Macrophage Colony-Stimulation Factor–Based Antitumor Vaccine

Filipazzi, Paola; Valenti, Roberta; Huber, Veronica; Pilla, Lorenzo; Canese, Paola; Iero, Manuela; Castelli, Chiara; Mariani, Luigi; Parmiani, Giorgio; Rivoltini, Licia

doi:10.1200/jco.2006.08.5829

Cited by 599 publications

(537 citation statements)

References 33 publications

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“…However, accumulating studies show that these factors also promote the expansion of myeloid suppressive components, with undesirable consequences on tumor antigen-specific immune responses [182]. For instance, GM-CSF-based anti-tumor vaccine to human metastatic melanoma patients induced a subset of immunosuppressive MDSCs that involved TGFβ secretion [183]. GM-CSF may increase immune responses when administered at low doses, while causing an opposite effect at high doses [182].…”

Section: Regulation Of Neutrophil Mobilization Recruitment and Activmentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

342

261

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Neutrophils are myeloid cells that constitute 50-70 % of all white blood cells in the human circulation. Traditionally, neutrophils are viewed as the first line of defense against infections and as a major component of the inflammatory process. In addition, accumulating evidence suggest that neutrophils may also play a key role in multiple aspects of cancer biology. The possible involvement of neutrophils in cancer prevention and promotion was already suggested more than half a century ago, however, despite being the major component of the immune system, their contribution has often been overshadowed by other immune components such as lymphocytes and macrophages. Neutrophils seem to have conflicting functions in cancer and can be classified into anti-tumor (N1) and pro-tumor (N2) sub-populations. The aim of this review is to discuss the varying nature of neutrophil function in the cancer microenvironment with a specific emphasis on the mechanisms that regulate neutrophil mobilization, recruitment and activation.

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Section: Regulation Of Neutrophil Mobilization Recruitment and Activmentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

342

261

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“…In cancer patients, the number of circulating MDSCs significantly increases compared to healthy subjects 38 . Our study, however, is the first demonstration in a cancer model that TLR stimulation leads to local MDSCs expansion, accounting for enhanced tumor growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…We found that stimulation of TLR7 expressed by adenocarcinoma cells modulated the immune infiltrate, leading to a significant expansion in MDSCs, associated with an increased secretion of CCL2 and GM-CSF in the tumor microenvironment. Both these cytokines are known to play a key role in the recruitment of MDSCs 38,41,42 . Indeed, the absence of CCL2 production by cancer cells considerably reduces the recruitment of MDSCs into tumors 42 .…”

Section: Discussionmentioning

confidence: 99%

Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells

et al. 2018

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In non-small cell lung carcinoma (NSCLC), stimulation of toll-like receptor 7 (TLR7), a receptor for single stranded RNA, is linked to tumor progression and resistance to anticancer chemotherapy. However, the mechanism of this effect has been elusive. Here, using a murine model of lung adenocarcinoma, we demonstrate a key role for TLR7 expressed by malignant (rather than by stromal and immune) cells, in the recruitment of myeloid derived suppressor cells (MDSCs), induced after TLR7 stimulation, resulting in accelerated tumor growth and metastasis. In adenocarcinoma patients, high TLR7 expression on malignant cells was associated with poor clinical outcome, as well as with a gene expression signature linked to aggressiveness and metastastic dissemination with high abundance of mRNA encoding intercellular adhesion molecule 1 (ICAM-1), cytokeratins 7 and 19 (KRT-7 and 19), syndecan 4 (SDC4), and p53. In addition, lung tumors expressing high levels of TLR7 have a phenotype of epithelial mesenchymal transition with high expression of vimentin and low abundance of E-cadherin. These data reveal a crucial role for cancer cell-intrinsic TLR7 expression in lung adenocarcinoma progression.

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“…In melanoma patients, another subset of monocytic MDSC has been identified with CD14 + CD11b + HLA-DRl ow/neg phenotype [109,110]. Two main subpopulations of MDSCs taking part in suppression of immune system in melanoma and colon cancer are: CD14 + monocytes and CD15 + neutrophils and both of these cell types express IL-4 receptor (CD124).…”

Section: Myeloid-derived Suppressor Cells In Tumor Environmentmentioning

confidence: 99%

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

Kumar

2012

Purinergic Signalling

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Cancer is a chronic disease and its pathogenesis is well correlated with infection and inflammation. Adenosine is a purine nucleoside, which is produced under metabolic stress like hypoxic conditions. Acute or chronic inflammatory conditions lead to the release of precursor adenine nucleotides (adenosine triphosphate (ATP), adenosien diphosphate (ADP) and adenosine monophosphate (AMP)) from cells, which are extracellularly catabolized into adenosine by extracellular ectonucleotidases, i.e., CD39 or nucleoside triphosphate dephosphorylase (NTPD) and CD73 or 5′-ectonucleotidase. It is now well-known that adenosine is secreted by cancer as well as immune cells during tumor pathogenesis under metabolic stress or hypoxia. Once adenosine is released into the extracellular environment, it exerts various immunomodulatory effects via adenosine receptors (A 1 , A 2A , A 2B , and A 3 ) expressed on various immune cells (i.e., macrophages, myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, dendritic cells (DCs), T cells, regulatory T cell (T regs ), etc.), which play very important roles in the pathogenesis of cancer. This review is intended to summarize the role of inflammation and adenosine in the immunopathogenesis of tumor along with regulation of tumor-specific immune response and its modulation as an adjunct approach to tumor immunotherapy.

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Identification of a New Subset of Myeloid Suppressor Cells in Peripheral Blood of Melanoma Patients With Modulation by a Granulocyte-Macrophage Colony-Stimulation Factor–Based Antitumor Vaccine

Abstract: CD14+HLA-DR-/lo cells exerting TGF-beta-mediated immune suppression represent a new subset of MSC potentially expandable by the administration of GM-CSF-based vaccines in metastatic melanoma patients.

Cited by 599 publications

References 33 publications

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells

Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

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