Tumor-Associated Neutrophils in Cancer: Going Pro

Wu, Lingyun; Saxena, Sugandha; Awaji, Mohammad; Singh, Rakesh K.

doi:10.3390/cancers11040564

Cited by 271 publications

(259 citation statements)

References 159 publications

Supporting

Mentioning

236

Contrasting

Order By: Relevance

“…Previously, two different neutrophil subpopulations were identified in lung tumor tissue, namely anti-tumorigenic, N1, and pro-tumorigenic, N2 PMNs, the latter accumulated as a result of increased TGFβ in the tumor microenvironment [12]. These descriptors have been expanded based upon context-specific neutrophil roles [21,35]. We found that, although BM-PCa increased neutrophil expression of TβRI, this increase had little impact on neutrophil-mediated PCa apoptosis despite increasing neutrophil viability.…”

Section: Discussionmentioning

confidence: 74%

“…Previous evidence in other cancer types has demonstrated that cancer-induced neutrophil ROS and NETs contribute to tumor proliferation, demonstrated in other cancer types [19][20][21]. However, the consequences of neutrophil activation and direct neutrophil-BM-PCa interactions on tumor growth have not been fully explored.…”

Section: Neutrophils Regulate Pca Growth In Vitro Independently Of Tgfβmentioning

confidence: 99%

See 1 more Smart Citation

Neutrophils are mediators of metastatic prostate cancer progression in bone

Costanzo-Garvey

Keeley

Case

et al. 2020

Cancer Immunol Immunother

View full text Add to dashboard Cite

Bone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that PCa growth in bone contributes to response to immunotherapy. We found that: (1) PCa stimulates recruitment of neutrophils, the most abundant immune cell in bone, and (2) that neutrophils heavily infiltrate regions of prostate tumor in bone of BM-PCa patients. Based on these findings, we examined the impact of direct neutrophilprostate cancer interactions on prostate cancer growth. Bone marrow neutrophils directly induced apoptosis of PCa in vitro and in vivo, such that neutrophil depletion in bone metastasis models enhanced BM-PCa growth. Neutrophil-mediated PCa killing was found to be mediated by suppression of STAT5, a transcription factor shown to promote PCa progression. However, as the tumor progressed in bone over time, neutrophils from late-stage bone tumors failed to elicit cytotoxic effector responses to PCa. These findings are the first to demonstrate that bone-resident neutrophils inhibit PCa and that BM-PCa are able to progress via evasion of neutrophil-mediated killing. Enhancing neutrophil cytotoxicity in bone may present a novel therapeutic option for bone metastatic prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Neutrophils Regulate Pca Growth In Vitro Independently Of Tgfβmentioning

confidence: 99%

Neutrophils are mediators of metastatic prostate cancer progression in bone

Costanzo-Garvey

Keeley

Case

et al. 2020

Cancer Immunol Immunother

View full text Add to dashboard Cite

show abstract

“…Several studies have provided compelling evidence for neutrophils' protumorigenic role, while others have advocated for neutrophils antitumor and antimetastatic potential . It is now generally accepted that neutrophils can acquire both pro‐ or antitumor function as part of an immunosuppressive switch occurring in cancer …”

Section: Introductionmentioning

confidence: 99%

“…8,9 It is now generally accepted that neutrophils can acquire both pro-or antitumor function as part of an immunosuppressive switch occurring in cancer. 10,11 Neutrophilia has been extensively described in cancer patients, but no clear correlation between absolute neutrophil count (ANC) and prognosis has been so far validated. 12,13 In contrast, the neutrophil-to-lymphocyte ratio (NLR) has been introduced as a strong prognostic factor for overall survival in many tumor types.…”

Section: Introductionmentioning

confidence: 99%

Circulating neutrophil subsets in advanced lung cancer patients exhibit unique immune signature and relate to prognosis

Shaul¹,

Eyal²,

Guglietta

et al. 2020

FASEB j.

View full text Add to dashboard Cite

The accumulation of circulating low‐density neutrophils (LDN) has been described in cancer patients and associated with tumor‐supportive properties, as opposed to the high‐density neutrophils (HDN). Here we aimed to evaluate the clinical significance of circulating LDN in lung cancer patients, and further assessed its diagnostic vs prognostic value. Using mass cytometry (CyTOF), we identified major subpopulations within the circulating LDN/HDN subsets and determined phenotypic modulations of these subsets along tumor progression. LDN were highly enriched in the low‐density (LD) fraction of advanced lung cancer patients (median 7.0%; range 0.2%‐80%, n = 64), but not in early stage patients (0.7%; 0.05%‐6%; n = 35), healthy individuals (0.8%; 0%‐3.5%; n = 15), or stable chronic obstructive pulmonary disease (COPD) patients (1.2%; 0.3%‐7.4%, n = 13). Elevated LDN (>10%) remarkably related with poorer prognosis in late stage patients. We identified three main neutrophil subsets which proportions are markedly modified in cancer patients, with CD66b+/CD10low/CXCR4+/PDL1inter subset almost exclusively found in advanced lung cancer patients. We found substantial variability in subsets between patients, and demonstrated that HDN and LDN retain a degree of inherent spontaneous plasticity. Deep phenotypic characterization of cancer‐related circulating neutrophils and their modulation along tumor progression is an important advancement in understanding the role of myeloid cells in lung cancer.

show abstract

“…More recently, Hanahan and Weinberg have highlighted the significance of inflammation as an enabling hallmark in their updated version of 'Hallmarks of Cancer' [2]. Inflammatory cells within the tumour microenvironment play a role in promoting tumour progression and metastasis and a high index of innate immune cell infiltration is often associated with poor prognosis [3,4]. Moreover, it is known that inflammation caused by pre-existing chronic inflammatory conditions conveys a predisposition to cancer development (the 'extrinsic pathway'), whilst genetic events leading to neoplasia themselves promote the recruitment of inflammatory cells into tumours (the 'intrinsic pathway') [5].…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Elliot

Myllymäki

Feng

2020

Cells

View full text Add to dashboard Cite

The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level, providing novel insights into our understanding of cancer. Here we summarise the available transgenic zebrafish tumour models and discuss what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response towards transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour-associated macrophages and neutrophils in mammalian models and present evidence that supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to the signals that mediate leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells in zebrafish appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

show abstract

Tumor-Associated Neutrophils in Cancer: Going Pro

Cited by 271 publications

References 159 publications

Neutrophils are mediators of metastatic prostate cancer progression in bone

Neutrophils are mediators of metastatic prostate cancer progression in bone

Circulating neutrophil subsets in advanced lung cancer patients exhibit unique immune signature and relate to prognosis

Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Contact Info

Product

Resources

About