Algorithm Identifies Macrophage Population Associated with Recurrence

2008 ◽  
Vol 205 (6) ◽  
pp. 1261-1268 ◽  
Author(s):  
Thorsten Hagemann ◽  
Toby Lawrence ◽  
Iain McNeish ◽  
Kellie A. Charles ◽  
Hagen Kulbe ◽  
...  

The nuclear factor κB (NF-κB) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-κB in cancer in maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive “alternative” phenotype that requires IκB kinase β–mediated NF-κB activation. When NF-κB signaling is inhibited specifically in TAMs, they become cytotoxic to tumor cells and switch to a “classically” activated phenotype; IL-12high, major histocompatibility complex IIhigh, but IL-10low and arginase-1low. Targeting NF-κB signaling in TAMs also promotes regression of advanced tumors in vivo by induction of macrophage tumoricidal activity and activation of antitumor activity through IL-12–dependent NK cell recruitment. We provide a rationale for manipulating the phenotype of the abundant macrophage population already located within the tumor microenvironment; the potential to “re-educate” the tumor-promoting macrophage population may prove an effective and novel therapeutic approach for cancer that complements existing therapies.


2020 ◽  
Vol 11 (2) ◽  
pp. 85-91
Author(s):  
Rachma Greta Putri ◽  
Sari Eka Pratiwi ◽  
Didik Setyo Heriyanto ◽  
Danarto Danarto ◽  
Indwiani Astuti ◽  
...  

Latar Belakang: Gangguan regulasi mikroRNA(miR) dan inflamasi kronik dapat mengubah tumor menjadi karsinoma dan kanker dengan metastasis melalui perubahan seluler dan genomik. Lesi prekanker memiliki peluang 33,3 persen menjadi kanker. Penelitian ini bertujuan untuk mengkaji peran miR-155-5p terhadap mRNA SOCS1 dan populasi makrofag terhadap progresivitas penyakit yang berhubungan dengan Benign Prostate Hyperplasia (BPH), High Grade Prostatic Intraepithelial Neoplasia (HGPIN), dan Prostate Adenocarcinoma (PRAD). Metode: Penelitian ini merupakan penelitian potong lintang dengan 3 kelompok, yaitu BPH,HGPIN, dan PRAD. Sampel jaringan didapatkan dari Tindakan TURP. Ekspresi miR-155 dianalisis menggunakan qPCR dan dikalkulasi menggunakan metode Livak. Ekspresi mRNA SOCS-1 dianalisis menggunakan reverse transcriptase PCR. Penanda pan makrofag, anti CD-68 monoclonal antibody(MoAb) digunakan untuk mendeteksi populasi makrofag pada jaringan dengan imunohistokimia. Hasil: Ekspresi miR-155 lebih tinggi pada HGPIN dibandingkan BPH dan PRAD (p=0,14). Ekspresi mRNA SOCS1 pada HGPIN paling rendah diantara ketiga sampel (p=0,96). Terdapat korelasi negative antara miR-155 dan mRNA SOCS1 (p=0,02). Terdapat peningkatan persentase populasi makrofag yang signifikan pada HGPIN (6,03 persen) dibandingkan BPH (0.89 persen) dengan p=0,00. Kesimpulan: Pada penelitian ini, terdapat perubahan persentase makrofag dan miR-155 pada HGPIN. Variasi ekspresi miR-155 dan persentase populasi makrofag dapat disebabkan karena perubahan epigenetik. Oleh sebab itu, perlu penelitian lebih lanjut untuk memvalidasi hasil tersebut dan memahami  kemungkinan menjadi biomarker pada penyakit prekanker pada prostat. Kata Kunci: Prostatic Intaepithelial Neoplasia, miR-155, Makrofag   Abstract   Background: Impaired microRNA(miR) regulation and chronic inflammation could transform tumors into carcinoma and cancer by metastasis through cellular and genomic changes. Precancerous lesions have a 33.3 percent chance of becoming cancerous. This study investigated the role of miR-155 related to SOCS1 mRNA and macrophage population in disease progression associated  with Benign Prostate Hyperplasia (BPH), High-Grade Prostatic Intraepithelial Neoplasia (HGPIN), and Prostate Adenocarcinoma (PRAD). Methods: This was a cross-sectional study using three groups of samples, namely BPH, HGPIN, and PRAD. Tissue samples were obtained from TURP Action. The expression of miR-155 was analyzed using real-time qPCR and calculated using the Livak method. The expression of SOCS1 mRNA was analyzed using reverse transcriptase PCR. The macrophage pan-marker, anti-CD68 monoclonal antibody (MoAb), was used to detect macrophage population in tissues by immunohistochemistry. Results: The expression of miR-155 was higher in HGPIN than BPH and PRAD (p=0.14). The expression of SOCS1 mRNA in HGPIN was the lowest among the three samples (p=0.96). There was a negative correlation between miR-155 and SOCS1 mRNA (p=0.02). There was a significant increase in the percentage of the macrophage population in HGPIN (6.03 percent) compared to BPH (0.89 percent) with p=0.00. Conclusion: In this study, there were changes in the percentage of macrophage and miR-155 in HGPIN. The variation in miR-155 expression and the percentage of the macrophage may be caused by epigenetic changes. Therefore, further research is needed to validate these results and understand the possibility of being a biomarker in precancerous disease of the prostate. Keywords: Prostatic Intraepithelial Neoplasia, miR-155, Macrophage  


Oncotarget ◽  
2016 ◽  
Vol 7 (40) ◽  
pp. 65968-65981 ◽  
Author(s):  
Stefania Fiorcari ◽  
Rossana Maffei ◽  
Valentina Audrito ◽  
Silvia Martinelli ◽  
Elisa ten Hacken ◽  
...  

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Xiaojing Ma

The work by Etzerodt et al. in this issue of JEM (https://doi.org/10.1084/jem.20191869) identifies a distinct omentum-resident macrophage population of embryonic origin and demonstrates that these cells provide a niche for ovarian cancer metastasis and cancer stemness. This research opens up for many questions and therapeutic prospects.


2020 ◽  
Vol 41 (9) ◽  
pp. 1288-1295
Author(s):  
Kathryn Y. Noonan ◽  
Ivan A. Lopez ◽  
Gail Ishiyama ◽  
Akira Ishiyama

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
V. Helfinger ◽  
K. Palfi ◽  
A. Weigert ◽  
K. Schröder

The family of NADPH oxidases represents an important source of reactive oxygen species (ROS) within the cell. Nox4 is a special member of this family as it constitutively produces H2O2 and its loss promotes inflammation. A major cellular component of inflammation is the macrophage population, which can be divided into several subpopulations depending on their phenotype, with proinflammatory M(LPS+IFNγ) and wound-healing M(IL4+IL13) macrophages being extremes of the functional spectrum. Whether Nox4 is expressed in macrophages is discussed controversially. Here, we show that macrophages besides a high level of Nox2 indeed express Nox4. As Nox4 contributes to differentiation of many cells, we hypothesize that Nox4 plays a role in determining the polarization and the phenotype of macrophages. In bone marrow-derived monocytes, ex vivo treatment with LPS/IFNγ or IL4/IL13 results in polarization of the cells into M(LPS+IFNγ) or M(IL4+IL13) macrophages, respectively. In this ex vivo setting, Nox4 deficiency reduces M(IL4+IL13) polarization and forces M(LPS+IFNγ). Nox4-/- M(LPS+IFNγ)-polarized macrophages express more Nox2 and produce more superoxide anions than wild type M(LPS+IFNγ)-polarized macrophages. Mechanistically, Nox4 deficiency reduces STAT6 activation and promotes NFκB activity, with the latter being responsible for the higher level of Nox2 in Nox4-deficient M(LPS+IFNγ)-polarized macrophages. According to those findings, in vivo, in a murine inflammation-driven fibrosarcoma model, Nox4 deficiency forces the expression of proinflammatory genes and cytokines, accompanied by an increase in the number of proinflammatory Ly6C+ macrophages in the tumors. Collectively, the data obtained in this study suggest an anti-inflammatory role for Nox4 in macrophages. Nox4 deficiency results in less M(IL4+IL13) polarization and suppression of NFκB activity in monocytes.


2019 ◽  
Vol 20 (10) ◽  
pp. 2474 ◽  
Author(s):  
Jonathan Yap ◽  
Hector A. Cabrera-Fuentes ◽  
Jason Irei ◽  
Derek J. Hausenloy ◽  
William A. Boisvert

Cardiovascular diseases are the leading cause of mortality worldwide. It is widely known that non-resolving inflammation results in atherosclerotic conditions, which are responsible for a host of downstream pathologies including thrombosis, myocardial infarction (MI), and neurovascular events. Macrophages, as part of the innate immune response, are among the most important cell types in every stage of atherosclerosis. In this review we discuss the principles governing macrophage function in the healthy and infarcted heart. More specifically, how cardiac macrophages participate in myocardial infarction as well as cardiac repair and remodeling. The intricate balance between phenotypically heterogeneous populations of macrophages in the heart have profound and highly orchestrated effects during different phases of myocardial infarction. In the early “inflammatory” stage of MI, resident cardiac macrophages are replaced by classically activated macrophages derived from the bone marrow and spleen. And while the macrophage population shifts towards an alternatively activated phenotype, the inflammatory response subsides giving way to the “reparative/proliferative” phase. Lastly, we describe the therapeutic potential of cardiac macrophages in the context of cell-mediated cardio-protection. Promising results demonstrate innovative concepts; one employing a subset of yolk sac-derived, cardiac macrophages that have complete restorative capacity in the injured myocardium of neonatal mice, and in another example, post-conditioning of cardiac macrophages with cardiosphere-derived cells significantly improved patient’s post-MI diagnoses.


1993 ◽  
Vol 24 (2) ◽  
pp. 139-151 ◽  
Author(s):  
Douglas J. Raburn ◽  
Arthur Coquelin ◽  
Adam J. Reinhart ◽  
James C. Hutson

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