Chemokine regulation of neutrophil function in tumors

Bonavita, Ornella; Massara, Matteo; Bonecchi, Raffaella

doi:10.1016/j.cytogfr.2016.03.012

Cited by 29 publications

(27 citation statements)

References 67 publications

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“…The contribution of neutrophils and macrophages to antitumor immunity remains controversial; numerous reports suggested that they display anti-and protumor effects. They alter the tumor environment by promoting angiogenesis, metastasis, tumor cell killing, and immunosuppression via the production of TGF-b, ROS, VEGF, and leukotrienes (39,47). TPT treatment did not enhance macrophage infiltration but slightly enhanced neutrophil infiltration into the tumor site ( Fig.…”

Section: Discussionmentioning

confidence: 95%

DNA-Containing Exosomes Derived from Cancer Cells Treated with Topotecan Activate a STING-Dependent Pathway and Reinforce Antitumor Immunity

Kitai

Kawasaki

Sueyoshi

et al. 2017

The Journal of Immunology

242

196

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Danger-associated molecular patterns derived from damaged or dying cells elicit inflammation and potentiate antitumor immune responses. In this article, we show that treatment of breast cancer cells with the antitumor agent topotecan (TPT), an inhibitor of topoisomerase I, induces danger-associated molecular pattern secretion that triggers dendritic cell (DC) activation and cytokine production. TPT administration inhibits tumor growth in tumor-bearing mice, which is accompanied by infiltration of activated DCs and CD8 T cells. These effects are abrogated in mice lacking STING, an essential molecule in cytosolic DNA-mediated innate immune responses. Furthermore, TPT-treated cancer cells release exosomes that contain DNA that activate DCs via STING signaling. These findings suggest that a STING-dependent pathway drives antitumor immunity by responding to tumor cell-derived DNA.

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Section: Discussionmentioning

confidence: 95%

DNA-Containing Exosomes Derived from Cancer Cells Treated with Topotecan Activate a STING-Dependent Pathway and Reinforce Antitumor Immunity

Kitai

Kawasaki

Sueyoshi

et al. 2017

The Journal of Immunology

242

196

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“…Moreover, neutrophils lacking ACKR2 had increased expression of the chemokine receptors Ccr1 , Ccr2 , and Ccr5 , a chemokine receptor profile again typical of activated neutrophils. Indeed, neutrophils express different pattern of chemokine receptors depending on their activation state 36 , 37 . Interferon-γ, the prototypic Th1 cytokine, upregulates the expression of the CC chemokine receptors CCR1 and CCR3 38 , and inflammatory stimuli such as lipopolysaccharide (LPS) induce CCR2 expression in neutrophils 39 .…”

Section: Discussionmentioning

confidence: 99%

“…Interferon-γ, the prototypic Th1 cytokine, upregulates the expression of the CC chemokine receptors CCR1 and CCR3 38 , and inflammatory stimuli such as lipopolysaccharide (LPS) induce CCR2 expression in neutrophils 39 . The expression of CC chemokine receptors by neutrophils is functionally relevant not only in terms of recruitment to the inflamed site but also in the activation of their effector functions such as respiratory burst, bacterial killing, and anti-metastatic activity 28 , 36 , 40 . In line with these data Ackr2-deficient neutrophils showed increased recruitment to the lungs (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity

et al. 2018

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Atypical chemokine receptors (ACKRs) are regulators of leukocyte traffic, inflammation, and immunity. ACKR2 is a scavenger for most inflammatory CC chemokines and is a negative regulator of inflammation. Here we report that ACKR2 is expressed in hematopoietic precursors and downregulated during myeloid differentiation. Genetic inactivation of ACKR2 results in increased levels of inflammatory chemokine receptors and release from the bone marrow of neutrophils with increased anti-metastatic activity. In a model of NeuT-driven primary mammary carcinogenesis ACKR2 deficiency is associated with increased primary tumor growth and protection against metastasis. ACKR2 deficiency results in neutrophil-mediated protection against metastasis in mice orthotopically transplanted with 4T1 mammary carcinoma and intravenously injected with B16F10 melanoma cell lines. Thus, ACKR2 is a key regulator (checkpoint) of mouse myeloid differentiation and function and its targeting unleashes the anti-metastatic activity of neutrophils in mice.

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“…Interestingly, two treatments, type I IFNs ( 65 ) and TGF-β targeting ( 56 ), that can promote neutrophil differentiation toward an anti-tumoral phenotype are inducing glioma regression. Current therapies may also be combined with treatments that promote selective recruitment of anti-tumoral neutrophils at the tumor site ( 66 ). Finally, the ability of neutrophils to migrate in the inflamed brain can be exploited to deliver anti-cancer drugs in gliomas after surgery, reducing regrowth of tumors ( 67 ).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Neutrophils in Gliomas

et al. 2017

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Neutrophils are the most abundant white blood cells and are the first recruited to inflammatory sites. Neutrophils are an important component of the tumor stroma and can exert both anti-tumoral and pro-tumoral activities, depending on their maturation and activation state. In human gliomas, the number of circulating and infiltrating neutrophils correlates with the severity of the disease, indicating a prognostic and possible pro-tumoral role for these leukocytes. In glioma preclinical models, neutrophils promote tumor growth and orchestrate the resistance to anti-angiogenic therapies. Nevertheless, recent data indicate that neutrophils can be activated to directly kill tumor cells or to orchestrate the anti-tumoral response. Here, we review current knowledge about the role of neutrophils in glioma and their possible involvement in new strategies to improve current cancer therapies.

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Chemokine regulation of neutrophil function in tumors

Cited by 29 publications

References 67 publications

DNA-Containing Exosomes Derived from Cancer Cells Treated with Topotecan Activate a STING-Dependent Pathway and Reinforce Antitumor Immunity

DNA-Containing Exosomes Derived from Cancer Cells Treated with Topotecan Activate a STING-Dependent Pathway and Reinforce Antitumor Immunity

ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti-metastatic activity

Neutrophils in Gliomas

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