Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes

Kowanetz, Marcin; Wu, Xiumin; Lee, John; Tan, Martha; Hagenbeek, Thijs J.; Qu, Xueping; Yu, Lanlan; Ross, Jed; Korsisaari, Nina; Cao, Tiesen; Bou-Reslan, Hani; Kallop, Dara; Weimer, Robby M.; Ludlam, Mary J. C.; Kaminker, Joshua S.; Modrušan, Zora; Bruggen, Nicholas van; Peale, Franklin; Carano, Richard A.D.; Meng, Y. Gloria; Ferrara, Napoleone

doi:10.1073/pnas.1015855107

Cited by 571 publications

(619 citation statements)

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“…While chronic inflammation may promote tumorigenesis [5,20], the tumor cells themselves also attract immune cells through the secretion of a wide range of chemokines such as IL-8 (CXCL8 in human/CXCL2 in mouse), CCL2 (MCP-1), CCL3 (MIP-1α), CCL5 (RANTES), CXCL6 (huGCP-2), and KC (CXCL1), and cytokines such as IL-1β, IL-6, TNFα, GM-CSF, and G-CSF, thereby inducing inflammation [21][22][23][24][25][26][27][28][29][30][31][32]. Cytokines from tumors may regulate tumor growth or modify the anti-tumor immune responses [33][34][35][36].…”

Section: Niche-dependent Neutrophil Functionmentioning

confidence: 99%

“…On the one hand, G-CSF is an essential cytokine for mobilization of neutrophils, and under certain conditions, activates them. On the other hand, G-CSF may polarize granulocytes to promote tumor growth and metastasis [26]. These seemingly conflicting roles played by both neutrophils and the tumor-derived chemokines, put forth the question of what determines the overall contribution of neutrophils to cancer?…”

Section: Neutrophil Activation In Cancermentioning

confidence: 99%

“…Still, while these studies do not implicate neutrophils in the process of priming the pre-metastatic niche, the fact the neutrophil chemoattractants such as S100A8 and S100A9 [301] are available in the pre-metastatic lung, together with our own observations [32] showing neutrophils accumulating early in the pre-metastatic lung, support the notion that neutrophils may contribute to the formation of the pre-metastatic niche. Furthermore, Kowanetz et al [26] showed that depletion of Gr1 + or Ly6G + cells from the pre-metastatic lung results in reduced metastasis. Similarly, Sceneay et al [304] also observed increased numbers of granulocytic CD11b + Ly6C med Ly6G + myeloid cells in the pre-metastastic lungs in mice injected with melanoma or breast carcinoma cells with a concomitant reduction in the cytotoxic activity of NK cells [304].…”

Section: Neutrophils In Pre-metastatic Organs -The "Seed and Soil" Hymentioning

confidence: 99%

“…In parallel, the granulocytes are often activated in cancer patients with a concomitant increase in H 2 O 2 production [278]. G-CSF is often secreted by tumor cells [26,174,189,190,194,198,276,[352][353][354][355][356][357][358][359] and is preferentially observed in dedifferentiated or poorly differentiated tumors [360,361,354,190]. Elevated G-CSF blood concentrations in cancer patients have been associated with poor clinical outcome [174,194,198,276,352,355,356].…”

Section: Prognostic Values Of Neutrophils and Other Myeloid Subtypesmentioning

confidence: 99%

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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: Niche-dependent Neutrophil Functionmentioning

confidence: 99%

Section: Neutrophil Activation In Cancermentioning

confidence: 99%

Section: Neutrophils In Pre-metastatic Organs -The "Seed and Soil" Hymentioning

confidence: 99%

Section: Prognostic Values Of Neutrophils and Other Myeloid Subtypesmentioning

confidence: 99%

See 2 more Smart Citations

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

342

261

View full text Add to dashboard Cite

show abstract

“…Clinical support for a role of neutrophils in chemotherapy response comes from observations in a variety of cancer patients, such as breast and non-small cell lung cancer patients, where chemotherapyinduced neutropenia is associated with better patient prognosis [46,47]. We and others have established a metastasis-promoting role for neutrophils in breast and melanoma models [48][49][50]. Therefore, targeting neutrophils or their mediators may synergize with chemotherapeutics to specifically decrease metastasis.…”

Section: Innate Immune Cellsmentioning

confidence: 97%

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Coffelt

Visser

2015

Trends in Immunology

125

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SummaryConventional anti-cancer therapies, such as chemotherapy, radiotherapy and targeted therapy, are designed to kill cancer cells. Yet, the efficacy of anti-cancer therapies is not only determined by their direct effects on cancer cells, but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit a number of changes in immune-related parameters including the composition, phenotype and function of immune cells. In this review, we discuss the impact of innate and adaptive immune cells on the success of anti-cancer therapy, we examine the opportunities to exploit host immune responses to boost tumor clearing and we highlight the challenges facing the treatment of advanced metastatic disease. Then and now: The link between the immune system and anti-cancer therapiesThe relationship between anti-cancer therapies and the immune system is as old as the invention of anti-cancer therapies themselves. After the use of mustard gas in the trenches of World War I, a seminal observation was made that some exposed soldiers displayed severe loss of bone marrow and lymph node cells [1]. This observation then spurred the idea that the anti-proliferative capacity of mustard gas may also slow the growth of cancer cells.Experiments carried out in mice transplanted with lymphoid tumors were convincing enough to treat a lymphoma patient [2], and these events initiated the standardized treatment of cancer patients with chemotherapy [3,4].Fast forward 100 years later. The influence of immune cells on tumor progression and metastasis is well established [5], and an appreciation for the immune system's impact during conventional anti-cancer therapy treatment is growing. Recent seminal advances indicate that immune cells can shape the outcome of various anti-cancer therapies. As such, 2 immune cells and their molecular mediators have evolved into bona vide targets of therapeutic manipulation in cancer patients. The recent breakthrough of immunotherapeutics that inhibit negative immune regulatory pathways, such as anti-CTLA4 and anti-PD1, has initiated a new era in the treatment of cancer [6]. In parallel, immunomodulatory strategies aimed at dampening pro-tumor functions of immune cells are currently being tested in cancer patients [7]. Immune cells also function as reliable biomarkers, since their abundance or activation status often predicts how well patients respond to a particular treatment regimen.Here, we review these novel experimental and clinical insights, highlighting potential implications for the development of synergistic therapies designed to combat primary tumors and, more importantly, metastatic disease. The pros and cons of experimental mouse modelsResearch questions aimed at understanding the role of immune cells during anti-cancer therapy require models that mirror the complex interactions between the immune system and diverse forms of human cancers. Transplantable cancer cell line models and carcinogeninduced cancer models are the most frequently used for these purposes. However...

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Neutrophil and Nanoparticles Delivery to Tumor: Is It Going to Carry That Weight?

Vishnevskiy

Garanina

Chernysheva

et al. 2021

Adv Healthcare Materials

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The application of cell carriers for transporting nanodrugs to the tumor draws much attention as the alternative to the passive drug delivery. In this concept, the neutrophil (NΦ) is of special interest as this cell is able to uptake nanoparticles (NPs) and cross the vascular barrier in response to tumor signaling. There is a growing body of literature describing NP–NΦ interactions in vitro and in vivo that demonstrates the opportunity of using these cells to improve the efficacy of cancer therapy. However, a number of conceptual and technical issues need to be resolved for translating the technology into clinics. The current review summarizes the recent advances and challenges associated with NP–NΦ interactions, with the special focus on the complex interplay between the NP internalization pathways and the modulation of NΦ activity, and its potential consequences for nanodrug delivery.

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Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes

Cited by 571 publications

References 50 publications

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Neutrophil and Nanoparticles Delivery to Tumor: Is It Going to Carry That Weight?

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