Neutrophil metabolism in the cancer context

Bodac, Anita; Meylan, Etienne

doi:10.1016/j.smim.2021.101583

Cited by 25 publications

(15 citation statements)

References 138 publications

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“…Inflammation is one of the hallmarks of cancer. Additionally, neutrophils are among the most important immune cells implicated in promoting tumor progression[ 40 , 41 ]. NETs participate in cancer progression by promoting the proliferation, invasion, metastasis and angiogenesis of cancer cells as well as thrombosis in numerous tumor types[ 42 - 44 ].…”

Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer

Li¹,

Zou²,

Yang³

et al. 2022

WJG

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BACKGROUND The development of venous thromboembolism (VTE) is associated with high mortality among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlate with the prothrombotic state in some diseases, but are rarely reported in GC patients. AIM To investigate the effect of NETs on the development of cancer-associated thrombosis in GC patients. METHODS The levels of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry, and immunofluorescence staining. NET generation and hypercoagulation of platelets and endothelial cells (ECs) in vitro were observed by immunofluorescence staining. NET procoagulant activity (PCA) was determined by fibrin formation and thrombin–antithrombin complex (TAT) assays. Thrombosis in vivo was measured in a murine model induced by flow stenosis in the inferior vena cava (IVC). RESULTS NETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies showed that GC cells and their conditioned medium, but not gastric mucosal epithelial cells, stimulated NET release from neutrophils. In addition, NETs induced a hypercoagulable state of platelets by upregulating the expression of phosphatidylserine and P-selectin on the cells. Furthermore, NETs stimulated the adhesion of normal platelets on glass surfaces. Similarly, NETs triggered the conversion of ECs to hypercoagulable phenotypes by downregulating the expression of their intercellular tight junctions but upregulating that of tissue factor. Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin formation and the TAT complex. In the models of IVC stenosis, tumor-bearing mice showed a stronger ability to form thrombi, and NETs abundantly accumulated in the thrombi of tumor-bearing mice compared with control mice. Notably, the combination of deoxyribonuclease I, activated protein C, and sivelestat markedly abolished the PCA of NETs. CONCLUSION GC-induced NETs strongly increased the risk of VTE development both in vitro and in vivo . NETs are potential therapeutic targets in the prevention and treatment of VTE in GC patients.

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Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer

Li¹,

Zou²,

Yang³

et al. 2022

WJG

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“…The potential protective role of CD8+ T cells in ccRCC could be induced by altered expression of SAP18, compared with papRCC. SAP18 has been shown to modulate neutrophil migration and autophagy in tumor microenvironment (33); meanwhile neutrophil autophagy is highly related to the development of tumor (16). Both neutrophil migration and autophagy requires the metabolism of free fatty acid, in which ATG7 plays a critical role (17).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that SAP18 among those four potential prognostic biomarkers expressed by CD8+ T cells, SAP18 has been reported to be critical for autophagy (13,14), a manner for immune system cleaning out aged cells or injured cells. In tumor microenvironment, neutrophil metabolic function in autophagy and free fatty acid is considered to be important for malignancy (15,16). In ccRCC biopsies, SAP18-expressing CD8+ T cells were observed frequently to co-localize with neutrophils (Figure 6A).…”

Section: Sap18 Expressing Cd8+ T Cells Colocalize With Neutrophils In...mentioning

confidence: 99%

Tumor-Infiltrated CD8+ T Cell 10-Gene Signature Related to Clear Cell Renal Cell Carcinoma Prognosis

et al. 2022

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Clear cell renal cell carcinoma (ccRCC) usually affects multiple organs (e.g., bone and brain), and patient prognosis is usually poor. Although it is known that CD8+ T cell infiltration can potentially alleviate ccRCC progression, few studies have concentrated on the correlation between CD8+ T cell infiltration and ccRCC prognosis. In this study, ten genes expressed by infiltrated CD8+ T cells (i.e., AMD1, CCSER2, CIB1, DRAP1, HMGB2, HMGN1, NPIPB5, PTP4A2, RORA, and SAP18) were suggested as potential ccRCC prognostic biomarkers, by using next-generation sequencing (i.e. bulk sequencing and single-cell sequencing) of ccRCC, papillary renal cell carcinoma (papRCC), and control kidney biopsies. Specifically, we identified four genes (i.e., CCSER2, DRAP1, NPIPB5, and SAP18) as potential novel prognostic biomarkers for ccRCC. It is noteworthy that SAP18 derived from CD8+ T cells negatively correlates to Atg7+ neutrophils in ccRCC, compared with papRCC, indicating a potential decreased neutrophil metabolic function in autophagy and fatty acids. This study elucidated the protective role of infiltrated CD8+ T cells in ccRCC and identified ten candidate genes related to an improved prognosis in patients with ccRCC.

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“…MDSCs can impair the function of DCs, NK cells, and CTLs by overexpressing RONS, releasing IL-6 and IL-10, or depleting L-arginine (L-Arg), thus facilitating tumor escape [ 70 ]. Moreover, tumor-associated neutrophils (TANs) secrete arginase 1 (Arg-1) to degrade extracellular L-Arg, involved in the functional suppression of CD8 + T cells [ 71 ]. In this section, we mainly focus on published evidence related to immune escape during the early stages of tumorigenesis.…”

Section: Immunosuppressive Cell-induced Immune Escape In Early Tumori...mentioning

confidence: 99%

Tumor-Associated Inflammation: The Tumor-Promoting Immunity in the Early Stages of Tumorigenesis

Qiu

et al. 2022

Journal of Immunology Research

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Tumorigenesis is a multistage progressive oncogenic process caused by alterations in the structure and expression level of multiple genes. Normal cells are continuously endowed with new capabilities in this evolution, leading to subsequent tumor formation. Immune cells are the most important components of inflammation, which is closely associated with tumorigenesis. There is a broad consensus in cancer research that inflammation and immune response facilitate tumor progression, infiltration, and metastasis via different mechanisms; however, their protumor effects are equally important in tumorigenesis at earlier stages. Previous studies have demonstrated that during the early stages of tumorigenesis, certain immune cells can promote the formation and proliferation of premalignant cells by inducing DNA damage and repair inhibition, releasing trophic/supporting signals, promoting immune escape, and activating inflammasomes, as well as enhance the characteristics of cancer stem cells. In this review, we focus on the potential mechanisms by which immune cells can promote tumor initiation and promotion in the early stages of tumorigenesis; furthermore, we discuss the interaction of the inflammatory environment and protumor immune cells with premalignant cells and cancer stem cells, as well as the possibility of early intervention in tumor formation by targeting these cellular mechanisms.

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Neutrophil metabolism in the cancer context

Cited by 25 publications

References 138 publications

Neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer

Neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer

Tumor-Infiltrated CD8+ T Cell 10-Gene Signature Related to Clear Cell Renal Cell Carcinoma Prognosis

Tumor-Associated Inflammation: The Tumor-Promoting Immunity in the Early Stages of Tumorigenesis

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