About this Research Topic
Neutrophils have one major function: to defend against pathogens. Neutrophils are equipped with a diverse antimicrobial armamentarium that can be broadly divided into oxygen-dependent and -independent pathways. Neutrophils sense and are activated by a broad spectrum of microbial motifs (e.g. bacterial and fungal cell wall products) and by endogenous products of cellular injury. During these states, multiple neutrophil effector functions can be activated and amplified to maximize host defense. Neutrophil extracellular traps (NETs) are a distinct mode of action of these cells, leading mostly to their death. This is characterized by extracellular release of strands of chromatin and neutrophil granular constituents that amplify host defense against extracellular microbes.
The traditional concept that neutrophils are a homogeneous population of terminally differentiated cells whose function is limited to anti-microbial protection is being gradually revised. Neutrophils have been shown to impact tumor biology in multiple ways. Seen in this light, what are the roles of neutrophils in the tumor microenvironment (TME)? On top of their potential direct effects on the cancer cells and TME immunity, it is likely that neutrophilic responses in the TME are in several respects off-target effects of responses to infection and may result in tissue injury and extracellular matrix remodeling, increase in oxidative stress, and stimulation of thrombosis and changes in vasculature.
While primed to respond to infection and injury, neutrophils can either be a friend or a foe in the context of cancer. Neutrophils can directly influence tumor cell biology and determine recruitment and activation of other immune cells in the TME. The anti-tumor role of neutrophils includes the potential to cause tumor cell lysis, and, in some contexts, enhancing cellular immunity against cancer. However, neutrophils can promote tumor growth and metastasis through a number of mechanisms including: NETosis, stimulation of thrombosis, and matrix remodeling; formation of neutrophil-platelet aggregates that facilitate metastasis; and inhibition of T cell responses critical for anti-tumor immunity. There is also growing appreciation of neutrophil heterogeneity and plasticity that can potentially be exploited therapeutically.
An obstacle to scientific progress and therapeutic development is the lack of tools to clearly identify and target specific granulocytic populations. Granulocytic myeloid-derived suppressor cells (PMN-MDSC) are broadly defined as immature granulocytic populations that are expanded by tumor-derived factors and suppress T cell responses. There is a clear overlap between PMN-MDSC and neutrophils. However, distinct from PMN-MDSC, is the potential of the TME to modify the phenotype of mature neutrophils in ways that can enhance or impair anti-tumor immunity. The role of mature neutrophils in the TME is under-explored relative to other innate immune cell populations. Growing evidence supports the hypothesis that mature neutrophils are recruited to and are modified by the TME, and that they act as key modulators of anti-tumor immunity that can be targeted therapeutically.
Our goal is to provide a state-of-the art review of important areas of current research in the field of neutrophils in cancer. This Research Topic will address controversies in this field, important gaps in knowledge, and proposed future directions. We welcome the submission of Original Research, Review, and opinion articles covering the following sub-topics:
1) Role of neutrophils in enhancing (friend) or obstructing (foe) anti-tumor immunity.
2) Effects of tumor-derived factors on granulopoiesis and neutrophil expansion and polarization.
3) Current and new methods for the characterization of neutrophil sub-populations in the tumor microenvironment and in the circulation in cancer.
4) Mechanisms by which neutrophils stimulate tumor progression and metastasis, such as angiogenesis, NETosis and matrix remodeling.
5) Novel approaches and therapies targeting neutrophils for cancer diagnosis and treatment.
The traditional concept that neutrophils are a homogeneous population of terminally differentiated cells whose function is limited to anti-microbial protection is being gradually revised. Neutrophils have been shown to impact tumor biology in multiple ways. Seen in this light, what are the roles of neutrophils in the tumor microenvironment (TME)? On top of their potential direct effects on the cancer cells and TME immunity, it is likely that neutrophilic responses in the TME are in several respects off-target effects of responses to infection and may result in tissue injury and extracellular matrix remodeling, increase in oxidative stress, and stimulation of thrombosis and changes in vasculature.
While primed to respond to infection and injury, neutrophils can either be a friend or a foe in the context of cancer. Neutrophils can directly influence tumor cell biology and determine recruitment and activation of other immune cells in the TME. The anti-tumor role of neutrophils includes the potential to cause tumor cell lysis, and, in some contexts, enhancing cellular immunity against cancer. However, neutrophils can promote tumor growth and metastasis through a number of mechanisms including: NETosis, stimulation of thrombosis, and matrix remodeling; formation of neutrophil-platelet aggregates that facilitate metastasis; and inhibition of T cell responses critical for anti-tumor immunity. There is also growing appreciation of neutrophil heterogeneity and plasticity that can potentially be exploited therapeutically.
An obstacle to scientific progress and therapeutic development is the lack of tools to clearly identify and target specific granulocytic populations. Granulocytic myeloid-derived suppressor cells (PMN-MDSC) are broadly defined as immature granulocytic populations that are expanded by tumor-derived factors and suppress T cell responses. There is a clear overlap between PMN-MDSC and neutrophils. However, distinct from PMN-MDSC, is the potential of the TME to modify the phenotype of mature neutrophils in ways that can enhance or impair anti-tumor immunity. The role of mature neutrophils in the TME is under-explored relative to other innate immune cell populations. Growing evidence supports the hypothesis that mature neutrophils are recruited to and are modified by the TME, and that they act as key modulators of anti-tumor immunity that can be targeted therapeutically.
Our goal is to provide a state-of-the art review of important areas of current research in the field of neutrophils in cancer. This Research Topic will address controversies in this field, important gaps in knowledge, and proposed future directions. We welcome the submission of Original Research, Review, and opinion articles covering the following sub-topics:
1) Role of neutrophils in enhancing (friend) or obstructing (foe) anti-tumor immunity.
2) Effects of tumor-derived factors on granulopoiesis and neutrophil expansion and polarization.
3) Current and new methods for the characterization of neutrophil sub-populations in the tumor microenvironment and in the circulation in cancer.
4) Mechanisms by which neutrophils stimulate tumor progression and metastasis, such as angiogenesis, NETosis and matrix remodeling.
5) Novel approaches and therapies targeting neutrophils for cancer diagnosis and treatment.
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