Abstract:
:Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice. Analysis of clinical biomarkers for kidney function revealed impaired creatinine clearance and elevated total protein levels in urine from tumor-bearing mice. Electron microscopy analysis of the kidneys from mice with cancer showed reversible pathological signs such as mesangial hypercellularity, while permanent damage such as fibrosis or necrosis was not observed. Removal of NETs by treatment with DNase I, or pharmacological inhibition of the enzyme peptidylarginine deiminase 4 (PAD4), was sufficient to restore renal function in mice with cancer. Tumor-induced systemic inflammation and impaired perfusion of peripheral vessels could be reverted by the PAD4 inhibitor. In conclusion, the current study identifies NETosis as a previously unknown cause of cancer-associated renal dysfunction and describes a novel promising approach to prevent renal failure in individuals with cancer.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Cedervall J,Dragomir A,Saupe F,Zhang Y,Ärnlöv J,Larsson E,Dimberg A,Larsson A,Olsson AKdoi
10.1080/2162402X.2017.1320009subject
Has Abstractpub_date
2017-04-20 00:00:00pages
e1320009issue
8eissn
2162-4011issn
2162-402Xpii
1320009journal_volume
6pub_type
杂志文章相关文献
OncoImmunology文献大全abstract::Immunotherapy with immune checkpoint molecule-specific monoclonal antibody have obtained encouraging results from preclinical studies and clinical trials, which promoted us to explore whether this kind of immunotherapy could be applicable to head and neck squamous cell carcinoma (HNSCC). Lymphocyte activation gene-3 (...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2016.1239005
更新日期:2016-10-07 00:00:00
abstract::A cancer-promoting role of fibrogenesis in the liver has long been speculated; however, the molecular mechanisms regarding this phenomenon are largely unknown. We demonstrated in our previous study that macrophage-derived S100A4 promotes liver fibrosis via activation of hepatic stellate cells; however, whether and how...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2020.1725355
更新日期:2020-02-14 00:00:00
abstract::Human pancreatic ductal adenocarcinoma (PDAC) exhibits marginal responses to anti-PD-1/PD-L1 immunotherapy and its mechanism remains poorly understood. We have investigated the effect of anti-PD-L1 and c-Myc inhibition in PDAC. Using 87 patients with PDAC from our hospital database we found a significant correlation b...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2019.1581529
更新日期:2019-03-01 00:00:00
abstract::Recent findings from our laboratory provide the first indication that overexpression of Bcl-2 in Eµ-myc transgenic cells enhances tumor immunosurveillance by inducing NKG2D ligands. Initial evidence suggests that this model is relevant to human patients. Thus, antitumor therapies that target Bcl-2 harbor the risk of r...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.19536
更新日期:2012-08-01 00:00:00
abstract::Esophageal cancer-related gene 4 (Ecrg4), a hormone-like peptide, is thought to be a tumor suppressor, however, little is known about the mechanism of how Ecrg4 suppresses tumorigenesis. Here, we show that the ecrg4 null glioma-initiating cell (GIC) line, which was generated from neural stem cells of ecrg4 knockout (K...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2016.1242547
更新日期:2016-10-14 00:00:00
abstract::Combination therapies with phosphoinositide 3-kinase (PI3K) inhibitors and trastuzumab (anti-human epidermal growth factor receptor [HER]2/neu antibody) are effective against HER2+ breast cancer. Isoform-selective PI3K inhibitors elicit anti-tumor immune responses that are distinct from those induced by inhibitors of ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1421890
更新日期:2018-01-16 00:00:00
abstract::Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lin...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1445459
更新日期:2018-03-27 00:00:00
abstract::Immunotherapy by chimeric antigen receptor (CAR)-modified T-cells has shown unprecedented clinical efficacy for hematological malignancies. Recently two CAR T-cell based therapeutics, Kymriah (Tisagenlecleucel) and Yescarta (Axicabtagene ciloleucel) were approved by the US Food and Drug Administration and by the Europ...
journal_title:Oncoimmunology
pub_type: 杂志文章,评审
doi:10.1080/2162402X.2020.1777064
更新日期:2020-06-10 00:00:00
abstract::A non-antigen specific immunotherapy consisting of repeated co-administration of poly-IC and blocking antibodies targeting the programmed cell death-1 (PD-1) pathway dramatically inhibits tumor development in several mouse models of cancer. Tumor-reactive CD8+ T cells mediate the antitumor effects mediated by PD-1 blo...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.28440
更新日期:2014-05-15 00:00:00
abstract::We have made major advances in the treatment of melanoma through the use of targeted therapy and immune checkpoint blockade; however, clinicians are posed with therapeutic dilemmas regarding timing and sequence of therapy. There is a growing appreciation of the impact of antitumor immune responses to these therapies, ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1136044
更新日期:2016-02-02 00:00:00
abstract::Immune tolerance induced by regulatory mechanisms is an integral and fundamental part of immunity. In therapeutic settings, however, tolerance may significantly limit efficacy. Here, we summarize possible strategies to enhance therapeutic antibody dependent cellular cytotoxicity by overcoming NK cell tolerance. ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1016708
更新日期:2015-04-02 00:00:00
abstract::The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway has emerged as a critical inhibitory pathway regulating T-cell response in non-small-cell lung cancer (NSCLC), and the development of PD-1/PD-L1 inhibitors has changed the landscape of NSCLC therapy. Nevertheless, the high degree of non-responders demons...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1315488
更新日期:2017-04-20 00:00:00
abstract::Immune adjuvants aimed at initiating or re-activating host immunity against poorly immunogenic cancers represent a potential tool for immunotherapy. By employing the natural killer T (NKT) cell agonist α-galactosylceramide in a whole tumor cell therapeutic vaccine approach, we have achieved potent suppression of estab...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.22615
更新日期:2013-01-01 00:00:00
abstract::Regulatory T cell (Treg) promote IL-17-mediated colon tumorigenesis in multiple intestinal neoplasia (Min) mice colonized with enterotoxigenic Bacteroides fragilis (ETBF). Although they retain their immunosuppressive function, mucosal Treg are instrumental to initiate ETBF-triggered IL-17 colitis by limiting the avail...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1118601
更新日期:2015-12-21 00:00:00
abstract::MDR1 is an ATP-dependent transmembrane transporter primarily studied for its role in the detoxification of tissues and for its implication in resistance of tumor cells to chemotherapy treatment. Several studies also report on its expression on immune cells where it plays a protective role from xenobiotics and toxins. ...
journal_title:Oncoimmunology
pub_type: 杂志文章,评审
doi:10.1080/2162402X.2018.1499388
更新日期:2018-09-06 00:00:00
abstract::Low expression of RhoGDI2 is associated with poor outcome in cancer patients. In animal models, RhoGDI2 suppresses lung metastasis by reducing the expression of the proteoglycan versican, whose levels portend poor patient prognosis. Versican promotes metastasis through enhanced tumor migration and creation of an infla...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.20594
更新日期:2012-10-01 00:00:00
abstract::The prostaglandin (PG) synthetase cyclooxygenase 2 (Cox-2) promotes tumorigenesis, tumor progression, and metastasis in a variety of human cancer entities including pancreatic ductal adenocarcinoma (PDAC). In this study, we demonstrate that in PDAC cells such as Colo357 cells, enhanced Cox-2 expression and increased r...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/2162402X.2014.988460
更新日期:2015-01-07 00:00:00
abstract::Immune responses to tumor antigens have been reported in cancer patients. However, the relevance of such spontaneous immune responses to the clinical course has not been studied extensively. We showed that the overall survival of patients with antibodies against NY-ESO-1 or XAGE1 (GAGED2a) antigen was prolonged in gas...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/21624011.2014.970032
更新日期:2014-12-21 00:00:00
abstract::Estrogen receptors have recently been demonstrated at the cell surface. Unlike nuclear receptors, they are able to trigger rapid responses inside the cells. In this study, we evaluated the presence and the possible role of autoantibodies specific to estrogen receptor (anti-ER Abs) in the peripheral blood of breast can...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1074375
更新日期:2015-08-12 00:00:00
abstract::The alarmin IL-33 is an IL-1 family member that stimulates pleiotropic immune reactions depending on the target tissue and microenvironmental factors. In this study, we have investigated the role of IL-33/ST2 axis in antitumor response to melanoma. Injection of IL-33 in mice-bearing subcutaneous B16.F10 melanoma resul...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2017.1317420
更新日期:2017-04-20 00:00:00
abstract::Analysis of PDL1 mRNA expression in ∼5,500 breast cancers showed PDL1 upregulation in 38% of basal tumors and 38% of inflammatory breast cancers (IBC). Upregulation, associated with signs of strong cytotoxic local immune response, was associated with a better survival in the basal or triple-negative subtypes, and with...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1085148
更新日期:2015-08-31 00:00:00
abstract::Interleukin (IL)-10 is a major cancer-related immunosuppressive factor, exhibiting a unique ability to hamper the maturation of dendritic cells (DCs). We have previously reported that IL-10 induces the conversion of activated, migratory CD1a+ DCs found in the human skin to CD14+CD141+ macrophage-like cells. Here, as a...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.23837
更新日期:2013-04-01 00:00:00
abstract::Tumor-associated macrophages play a central role in tumor progression and metastasis. Macrophages can also promote the resistance of malignant cells to chemotherapy by stimulating the upregulation of cytidine deaminase, an intracellular enzyme that catabolizes the active form of gemcitabine. Targeting macrophage-depen...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.27231
更新日期:2013-12-01 00:00:00
abstract::Although the proteasome inhibitor bortezomib has significantly improved the survival of patients with multiple myeloma (MM), the disease remains fatal as most patients eventually develop progressive disease. Recent data indicate that MM cells can evade bortezomib-induced cell death by undergoing autophagy as a consequ...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1534664
更新日期:2018-11-02 00:00:00
abstract::Interleukin (IL)-17A belongs to IL-17 superfamily and binds the heterodimeric IL-17 receptor (R)(IL-17RA/IL-17RC). IL-17A promotes germinal center (GC) formation in mouse models of autoimmune or infectious diseases, but the role of IL-17A/IL-17AR complex in human neoplastic GC is unknown. In this study, we investigate...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2015.1030560
更新日期:2015-06-19 00:00:00
abstract::Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in tumour biology, recent studies have demonstrated the presence of of CD4+ T cells, expressing both, Tbet and Foxp3. Although Tbet+Foxp3+ T cells are currently a subject of intense research, less is known about their biological function espe...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1456612
更新日期:2018-04-25 00:00:00
abstract::Objective:Ovarian cancer (OC) is often diagnosed at an advanced stage with two thirds of patients experiencing recurrent disease with a poor prognosis. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has shown curative potential in malignant melanoma, but has only been investigated scarcely in ot...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2018.1502905
更新日期:2018-09-26 00:00:00
abstract::To antagonize tumor-derived TGFβ contemporaneously to anticancer immunotherapy, we genetically engineered a fusion protein coupling IL-2 and the ectodomain of TGFβ receptor II (Fusion of Interleukin-2 and Soluble TGFβ receptor - a.k.a. FIST). FIST possesses intriguing gain-of-function properties and induces potent act...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.1.2.18458
更新日期:2012-03-01 00:00:00
abstract::Cancer immunotherapy continues to make headway as a treatment for advanced stage tumors, revealing an urgent need to understand the fundamentals of anti-tumor immune responses. Noteworthy is a scarcity of data pertaining to the breadth and specificity of tumor-specific T cell responses in metastatic breast cancer. Aut...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.1080/2162402X.2019.1685300
更新日期:2019-11-29 00:00:00
abstract::Interleukin-10 (IL-10) is a potent immunomodulatory cytokine, whose cellular targets have not yet been precisely identified. Dendritic cell (DC)-specific IL-10 receptor knockout mice exhibit exaggerated T-cell reactivation in the skin, highlighting a key role of DCs in the maintenance of local immune homeostasis, beyo...
journal_title:Oncoimmunology
pub_type: 杂志文章
doi:10.4161/onci.23186
更新日期:2013-03-01 00:00:00