Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells

Yang, Xiaowen; Ai, Walden; Asfaha, Samuel; Bhagat, Govind; Friedman, Richard A.; Jin, Guangchun; Park, Heuijoon; Shykind, Benjamin; Diacovo, Thomas G.; Falus, András; Wang, Yichen

doi:10.1038/nm.2278

Cited by 195 publications

(238 citation statements)

References 47 publications

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“…An example of this was shown in mice with chemically induced cancer crossed with histamine-deficient mice, where the lack of histamine stalled differentiation of immature neutrophils and increased tumor incidence and growth 75 . These data suggest that immature cells have independent functions from mature neutrophils.…”

Section: Neutrophil Retention and Release From Bone Marrowmentioning

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 Retention and Release From Bone Marrowmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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“…It has been known that monocyte-derived myeloid suppressor cells can suppress the anti-tumor activity of T-cells by producing IL-10. In an experimental model of chemical-induced carcinogenesis, histidine carboxylase (HDC)-deficient mice showed a severe tumor progressive phenotype [36], accompanied by a massive influx of CD11b + Gr-1 + monocytes and their impairment in maturation. An independent study revealed that vascular endothelial growth factor (VEGF) produced by the infiltrating Gr-1 + monocytes in mammary cancer promotes tumor metastasis [37] into the lung.…”

Section: Tumor Progressionmentioning

confidence: 99%

Monocytes in health and disease — Minireview

Karlmark

Tacke²,

Dunay³

2012

European Journal of Microbiology and Immunology

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“…Yang et al (7) observed an increased accumulation of immature CD11b + /Gr1 + myeloid cells during cancer progression in HDC 2/2 mice compared with HDC-sufficient mice and reported that HDC 2/2 mice were strikingly susceptible to chemically induced cancer. These investigators also reported that the exogenous administration of histamine to HDC 2/2 mice prevented the accumulation of immature myeloid cells (7). However, the detailed mechanisms by which histamine deficiency results in the accumulation of immature myeloid cells are largely unknown.…”

mentioning

confidence: 99%

Histamine Promotes the Development of Monocyte-Derived Dendritic Cells and Reduces Tumor Growth by Targeting the Myeloid NADPH Oxidase

Martner

Wiktorin

Lenox

et al. 2015

The Journal of Immunology

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The efficiency of immune-mediated clearance of cancer cells is hampered by immunosuppressive mediators in the malignant microenvironment, including NADPH oxidase–derived reactive oxygen species. We aimed at defining the effects of histamine, an inhibitor of the myeloid NADPH oxidase/NOX2, on the development of Ag-presenting dendritic cells (DCs) from myeloid precursors and the impact of these mechanisms for tumor growth. Histamine was found to promote the maturation of human DCs from monocytes by increasing the expression of HLA-DR and costimulatory molecules, which resulted in improved induction of Th cells with Th0 polarity. Experiments using wild-type and NOX2-deficient myelomonoblastic cells showed that histamine facilitated myeloid cell maturation only in cells capable of generating reactive oxygen species. Treatment of mice with histamine reduced the growth of murine EL-4 lymphomas in parallel with an increment of tumor-infiltrating DCs in NOX2-sufficient mice but not in NOX2-deficient (gp91phox−/−) mice. We propose that strategies to target the myeloid NADPH oxidase may facilitate the development of endogenous DCs in cancer.

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Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells

Cited by 195 publications

References 47 publications

Neutrophils in cancer: neutral no more

Neutrophils in cancer: neutral no more

Monocytes in health and disease — Minireview

Histamine Promotes the Development of Monocyte-Derived Dendritic Cells and Reduces Tumor Growth by Targeting the Myeloid NADPH Oxidase

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