Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer

Timaxian, Colin; Vogel, Christoph F.A.; Orcel, Charlotte; Vetter, Diana; Durochat, Camille; Chinal, Clarisse; Nguyen, Phuong Thao; Aknin, Marie-Laure; Mercier-Nomé, Françoise; Davy, Martin; Raymond‐Letron, Isabelle; Van, Thi Nhu Ngoc; Diermeier, Sarah D.; Godefroy, Anastasia; Gary‐Bobo, Magali; Molina, Franck; Balabanian, Karl; Lazennec, Gwendal

doi:10.3390/cancers13112584

Cited by 25 publications

(21 citation statements)

References 86 publications

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“…Even the same molecule often exerts different effects on diverse stages. Although CXCR2 promotes neutrophil migration into pro-cancer sites, knockdown of CXCR2 in neutrophils increases ROS production and exerts pro-cancer effect [ 38 ]. Thus, in future studies, genetically engineered mouse models (GEMMs) will be extremely valuable for research in the field of cancer-related neutrophil biology, as they enable neutrophils and neutrophil-derived factors to be manipulated as cancer arises de novo.…”

Section: Neutrophils In Carcinogenesismentioning

confidence: 99%

Neutrophils in cancer carcinogenesis and metastasis

2021

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In recent years, neutrophils have attracted increasing attention because of their cancer-promoting effects. An elevated neutrophil-to-lymphocyte ratio is considered a prognostic indicator for patients with cancer. Neutrophils are no longer regarded as innate immune cells with a single function, let alone bystanders in the pathological process of cancer. Their diversity and plasticity are being increasingly recognized. This review summarizes previous studies assessing the roles and mechanisms of neutrophils in cancer initiation, progression, metastasis and relapse. Although the findings are controversial, the fact that neutrophils play a dual role in promoting and suppressing cancer is undeniable. The plasticity of neutrophils allows them to adapt to different cancer microenvironments and exert different effects on cancer. Given the findings from our own research, we propose a reasonable hypothesis that neutrophils may be reprogrammed into a cancer-promoting state in the cancer microenvironment. This new perspective indicates that neutrophil reprogramming in the course of cancer treatment is a problem worthy of attention. Preventing or reversing the reprogramming of neutrophils may be a potential strategy for adjuvant cancer therapy.

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Section: Neutrophils In Carcinogenesismentioning

confidence: 99%

Neutrophils in cancer carcinogenesis and metastasis

2021

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“…Inhibition of CXCR2 in breast carcinoma models reduced the recruitment of neutrophils into the tumor mass and increased the efficacy of chemotherapy [138,139]. On the other hand, genetic deletion of CXCR2 in the PyMT (polyoma middle T oncogene) model of breast cancer resulted in increased infiltration of TANs and promotion of tumor growth [140].…”

Section: Role Of Chemokines In Neutrophil Activities In Cancermentioning

confidence: 99%

Chemokines as Regulators of Neutrophils: Focus on Tumors, Therapeutic Targeting, and Immunotherapy

Bonecchi

Mantovani

Jaillon

2022

Cancers

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Neutrophils are an important component of the tumor microenvironment, and their infiltration has been associated with a poor prognosis for most human tumors. However, neutrophils have been shown to be endowed with both protumor and antitumor activities, reflecting their heterogeneity and plasticity in cancer. A growing body of studies has demonstrated that chemokines and chemokine receptors, which are fundamental regulators of neutrophils trafficking, can affect neutrophil maturation and effector functions. Here, we review human and mouse data suggesting that targeting chemokines or chemokine receptors can modulate neutrophil activity and improve their antitumor properties and the efficiency of immunotherapy.

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“…Blockage of CXCLs/CXCR2 axis reduced myeloid cell influx in pancreatic ductal adenocarcinoma and improved prognosis [14]. In contrast, knockdown of CXCR2 in the PyMT breast cancer model rendered neutrophils with characteristics in favor of tumor progression [15]. The ELR motif in CXC chemokines seems to be indispensable, but not a sole prerequisite for receptor binding and neutrophil activation [16].…”

Section: Chemokinesmentioning

confidence: 99%

The Role of Post-Translational Modifications of Chemokines by CD26 in Cancer

Zutter

Damme

Struyf

2021

Cancers

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Chemokines are a large family of small chemotactic cytokines that fulfill a central function in cancer. Both tumor-promoting and -impeding roles have been ascribed to chemokines, which they exert in a direct or indirect manner. An important post-translational modification that regulates chemokine activity is the NH2-terminal truncation by peptidases. CD26 is a dipeptidyl peptidase (DPPIV), which typically clips a NH2-terminal dipeptide from the chemokine. With a certain degree of selectivity in terms of chemokine substrate, CD26 only recognizes chemokines with a penultimate proline or alanine. Chemokines can be protected against CD26 recognition by specific amino acid residues within the chemokine structure, by oligomerization or by binding to cellular glycosaminoglycans (GAGs). Upon truncation, the binding affinity for receptors and GAGs is altered, which influences chemokine function. The consequences of CD26-mediated clipping vary, as unchanged, enhanced, and reduced activities are reported. In tumors, CD26 most likely has the most profound effect on CXCL12 and the interferon (IFN)-inducible CXCR3 ligands, which are converted into receptor antagonists upon truncation. Depending on the tumor type, expression of CD26 is upregulated or downregulated and often results in the preferential generation of the chemokine isoform most favorable for tumor progression. Considering the tight relationship between chemokine sequence and chemokine binding specificity, molecules with the appropriate characteristics can be chemically engineered to provide innovative therapeutic strategies in a cancer setting.

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Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer

Cited by 25 publications

References 86 publications

Neutrophils in cancer carcinogenesis and metastasis

Neutrophils in cancer carcinogenesis and metastasis

Chemokines as Regulators of Neutrophils: Focus on Tumors, Therapeutic Targeting, and Immunotherapy

The Role of Post-Translational Modifications of Chemokines by CD26 in Cancer

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