Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice

Sawanobori, Yasushi; Ueha, Satoshi; Kurachi, Makoto; Shimaoka, Takeshi; Talmadge, James E.; Abe, Jun; Shono, Yusuke; Kitabatake, Masahiro; Kakimi, Kazuhiro; Mukaida, Naofumi; Matsushima, Kouji

doi:10.1182/blood-2008-01-136895

Cited by 334 publications

(306 citation statements)

References 56 publications

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“…Animal experiments in calves and mice have shown that a small pool of non-circulating neutrophils can survive in tissue for several days 80,81 . Neutrophils are also retained longer in tumors than in the spleen 82 , suggesting that the tumor microenvironment encourages their survival both locally and systemically. Indeed, pioneering work from Mantovani and his colleagues in the 1990s showed that many tumor-associated cytokines prolong neutrophil survival in culture 83 .…”

Section: Neutrophil Lifespanmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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SummaryNeutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view.The traditionally held belief that neutrophils are inert bystanders is being challenged by recent literature. Emerging evidence indicates that tumors manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumor behavior. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets. 2The name neutrophil -given to polymorphonuclear, granulocytic cells by Paul Ehrlich in the late 19th century -is based on the inability of these cells to retain acidic or basic dyes and for their preferential uptake of pH neutral dyes 1 . Although their neutral staining led to the identification of these cells, neutrophils in the cancer setting are anything but neutral.Neutrophils in tumor-bearing hosts can oppose or potentiate cancer progression. These two types of behavior are controlled by signals emanating from cancer cells or stromal cells within the tumor microenvironment, which educate neutrophils to execute the demise of the tumor or facilitate support networks that lead to its expansive spread. These functions can occur locally in or around the tumor microenvironment, as well as systemically in distant organs.Until the past few years, other immune cells such as macrophages have overshadowed the role of neutrophils in cancer. But recent studies and the development of new genetic tools have provided the cancer community with new insights into the profound influence of these dynamic cells by uncovering distinct capabilities for neutrophils throughout each step of carcinogenesis: from tumor initiation to primary tumor growth to metastasis.During these processes, neutrophils take on different phenotypes and sometimes opposing functions. Emerging evidence also indicates that these cells are highly influential, and are able to change the behavior of other tumor-associated cell types -primarily other immune cells. In this Review, we focus on how tumors manipulate the generation and release of neutrophils from the bone marrow. We discuss the mechanisms identified in animal models by which neutrophils participate in tumor initiation, growth and metastasis. Finally, we highlight the potential of these cells as clinical biomarkers and therapeutic targets. In humans, neutrophils are the most abundant immune cell population, representing 50-70% of all leukocytes. Over 10 11 neutrophils may be produced per day 2 , and tumors can increase this number by even more. Indeed, patients with various cancer types, including but not limited to breast, lung and colorectal cancer, often exhibit increased numbers of circulating neutrophils 3,4 . Recent studies have identified key pathways that tumors exploit to disrupt normal neutrophil homeostasis and these are discuss...

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Section: Neutrophil Lifespanmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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“…Major attractants of monocytic precursors are the CC-chemokines [27][28][29]. In a variety of human cancers, CCL2 and CCL5 levels are correlated with high numbers of intra-tumor myeloid cells [7,30,31].…”

Section: Chemokine Regulation Of Leukocyte Attraction Within Tumorsmentioning

confidence: 99%

“…Finally, there is evidence that CC and CXC chemokines are involved also in the attraction of Myeloid Derived Suppressor Cells (MDSC) in tumors [29]. MDSC are a heterogeneous population of immature cells with suppressive function, which includes myeloid-related and mononuclear phagocyte-related elements [42,43].…”

Section: Chemokine Regulation Of Leukocyte Attraction Within Tumorsmentioning

confidence: 99%

Chemokines in cancer related inflammation

Allavena

Germano

Marchesi

et al. 2011

Experimental Cell Research

197

137

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Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis.Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies

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“…TAMs produce various growth factors such as TGF-β and fibroblast growth factor (FGF) in addition to VEGF and prostaglandin [22,44]. Moreover, TAMs exhibit the properties of M2-polarized macrophages and express scavenger receptors and the mannose receptor [47]. Furthermore, they produce immunosuppressive molecules including IL-10, TGF-β, and arginase [47].…”

Section: Leukocytesmentioning

confidence: 99%

“…Moreover, TAMs exhibit the properties of M2-polarized macrophages and express scavenger receptors and the mannose receptor [47]. Furthermore, they produce immunosuppressive molecules including IL-10, TGF-β, and arginase [47]. These properties endow TAMs with an Mukaida 9 immunosuppressive capacity.…”

Section: Leukocytesmentioning

confidence: 99%