Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonist attenuate tumor growth via polarization of neutrophils toward an antitumor phenotype

Shrestha, Sanjeeb; Noh, Jae Myoung; Kim, Shin-Yeong; Ham, Hwa-Yong; Kim, Yeon-Ja; Yun, Young-Jin; Kim, Min-Ju; Kwon, Min-Soo; Song, Dong‐Keun; Hong, Chang-Won

doi:10.1080/2162402x.2015.1067744

Cited by 41 publications

(31 citation statements)

References 53 publications

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“…8 Additional polarization signals including angiotensin-II, type I IFNs and the proto-oncogene MET also have the ability to drive N2 or N1 phenotypes. [95][96][97] Transcriptomic analysis further confirmed that these N1 and N2 neutrophils represent different populations 98 and that N2 neutrophils differ from circulating PMN-MDSCs in tumor bearing mice. 14 Interestingly, TGF-also mediates the polarization of mature HDNs to mature LDNs in mice and has led to these population being termed N1c and N2c, respectively.…”

Section: N1/n2 Neutrophilsmentioning

confidence: 75%

“…Using blockade of TGF‐β, they provided in vivo evidence to demonstrate that mature TANs could alter their function locally transitioning from a protumoral phenotype (N2) to an antitumoral (N1) population . Additional polarization signals including angiotensin‐II, type I IFNs and the proto‐oncogene MET also have the ability to drive N2 or N1 phenotypes . Transcriptomic analysis further confirmed that these N1 and N2 neutrophils represent different populations and that N2 neutrophils differ from circulating PMN‐MDSCs in tumor bearing mice .…”

Section: Neutrophil Populations In Inflammatory Settingsmentioning

confidence: 97%

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Neutrophil heterogeneity: Bona fide subsets or polarization states?

Deniset

Kubes

2018

Journal of Leukocyte Biology

121

125

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Neutrophils are key components of the innate immune system that play important roles during infection, injury, and chronic disease. In recent years, neutrophil heterogeneity has become an emerging focus with accumulating evidence of neutrophil populations with distinct functions under both steady-state and pathologic conditions. Despite these advances, it remains unclear whether these different populations represent bona fide subsets or simply activation/polarization states in response to local cues. In this review, we summarize the varied neutrophils populations that have been described under both basal and during inflammation. We discuss the evidence that supports the existence of neutrophils subsets. Finally, we identify potential gaps in our knowledge that may further advance our current understanding of neutrophil heterogeneity.

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Section: N1/n2 Neutrophilsmentioning

confidence: 75%

Section: Neutrophil Populations In Inflammatory Settingsmentioning

confidence: 97%

Neutrophil heterogeneity: Bona fide subsets or polarization states?

Deniset

Kubes

2018

Journal of Leukocyte Biology

121

125

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“…35,36 However, we observed no changes in expression of PD-L1, MHC class I and MHC class II molecules associated with direct Tcell interaction. Interestingly, elderly neutrophils exhibited a hypersegmented nuclear morphology, a process dependent on mTOR pathway, 37 which mediates several other neutrophil functions including chemotaxis and cytokine production. Nuclear hypersegmentation is also a distinct characteristic of antitumoral neutrophils characterized by a marked cytotoxic and proinflammatory phenotype.…”

Section: Discussionmentioning

confidence: 99%

Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T‐ and B‐cell zones

et al. 2018

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The average age of the human population is rising, leading to an increasing burden of age-related diseases, including increased susceptibility to infection. However, immune function can decrease with age which could impact on processes that require a functional immune system. Aging is also characterized by chronic low-grade inflammation which could further impact immune cell function. While changes to neutrophils in blood during aging have been described, little is known in aging lymphoid organs. This study used female C57BL/6J mice comparing bone marrow (BM), spleen and lymph nodes from young mice aged 2-3 months (equivalent to 18 human years) with healthy elderly mice aged 22-24 months (equivalent to 60-70 human years). Neutrophil proportions increased in BM and secondary lymphoid organs of elderly mice relative to their younger counterparts and presented an atypical phenotype. Interestingly, neutrophils from elderly spleen and lymph nodes were long lived (with decreased apoptosis via Annexin V staining and increased proportion of BrdU mature cells) with splenic neutrophils also demonstrating a hypersegmented morphology. Furthermore, splenic neutrophils of elderly mice expressed a mixed phenotype with increased expression of activation markers, CD11b and ICAM-1, increased proinflammatory TNFα, yet increased anti-inflammatory transforming growth factor-beta. Elderly splenic architecture was compromised, as the marginal zone (required for clearing infections) was contracted. Moreover, neutrophils from elderly but not young mice accumulated in lymph node and splenic T- and B-cell zones. Overall, the expansion of functionally compromised neutrophils could contribute to increased susceptibility to infection observed in the elderly.

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“…Neutrophils were isolated from venous blood by double density gradient method using histopaque 1077 and 5% dextran [2].…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Dataset on the changes of neutrophils treated with retinoic acid

et al. 2017

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The data presented in this article are related to the research article entitled “Retinoic acid induces hypersegmentation and enhances cytotoxicity of neutrophils against cancer cells” (S. Shrestha, S.Y. Kim, Y.J. Young, J.K. Kim, J.M. Lee, M. Shin, D.K. Song, C.W. Hong, 2017) [1]. This article complements the potential of retinoic acid to induce changes in effector function of human neutrophils. Here the datasets describe the rate of apoptosis, changes in numbers of nuclear lobes, and the expressions of surface markers in human neutrophils in presence or absence of retinoic acid. The tumor growth in recipient mice with adoptive transfer of retinoic acid-treated neutrophils was evaluated. The included data is made publicly available to criticism and extended analysis.

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Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonist attenuate tumor growth via polarization of neutrophils toward an antitumor phenotype

Cited by 41 publications

References 53 publications

Neutrophil heterogeneity: Bona fide subsets or polarization states?

Neutrophil heterogeneity: Bona fide subsets or polarization states?

Aged neutrophils accumulate in lymphoid tissues from healthy elderly mice and infiltrate T‐ and B‐cell zones

Dataset on the changes of neutrophils treated with retinoic acid

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