TIE2-expressing monocytes and M2-polarized macrophages impact survival and correlate with angiogenesis in adenocarcinoma of the pancreas

Atanasov, Georgi; Pötner, Charlotte; Aust, Gabriela; Schierle, Katrin; Dietel, Corinna; Benzing, Christian; Krenzien, Felix; Bartels, Michael; Eichfeld, U; Schmelzle, Moritz; Bahra, Marcus; Pascher, Andreas; Wiltberger, Georg

doi:10.18632/oncotarget.25690

Cited by 40 publications

(31 citation statements)

References 27 publications

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“…Interestingly, the tissueinfiltrating fraction of TEMs, which promotes angiogenesis and carcinogenesis, is localized only in the tumor microenvironment and not in healthy tissues [17,18]. In line with this, our data demonstrated significant influence of TEMs on patient outcome in other cancer types [19][20][21]. Thus, the study of TEMs in HCC may identify attractive targets for immunologic checkpoint inhibition.…”

Section: Introductionsupporting

confidence: 83%

Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

et al. 2019

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Background: Tumor escape mechanisms mediated in the tumor microenvironment can significantly reduce the capacity of the anti-tumor function of the immune system. TIE2-expressing monocytes (TEMs), related angiopoietins, and tumor necrosis are considered to have a key role in this process. We aimed to investigate the abundance and clinical significance of these biomarkers in hepatocellular carcinoma (HCC). Methods: In this retrospective study, 58 HCC patients received surgery with a curative intent. The abundance of TEMs, angiopoietin-1 and-2 were detected in tumor specimens of the HCC patients (n = 58), and together with the occurrence of histologic tumor necrosis, were associated with established clinicopathological characteristics and survival. Results: Patients with HCC characterized by necrosis and TEMs revealed reduced both overall survival and recurrence-free survival (all p < 0.05). Angiopoietins and TEMs were associated with metastatic and recurrent HCC. Furthermore, the formation of histologic tumor necrosis was associated with advanced tumor stage and density of TEMs (all p < 0.05). Conclusions: Histologic tumor necrosis, TEMs, and related angiopoietins were associated with multiple HCC parameters and patient survival. The tumor necrosis-TEM-angiopoietin axis may offer a novel diagnostic modality to predict patient outcome after surgery for HCC.

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Section: Introductionsupporting

confidence: 83%

Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

et al. 2019

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“…Quantification was performed as described [13]. In brief, tumour-infiltrating immune cells were categorized as negative/absent in up to 5% positive cells (0–5% positive cells, score 0) and positive/present (> 5% positive cells, score 1).…”

Section: Methodsmentioning

confidence: 99%

Immunologic cellular characteristics of the tumour microenvironment of hepatocellular carcinoma drive patient outcomes

et al. 2019

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Background Anti-tumour immune competence has an impact in hepatocarcinogenesis and success of anti-cancer therapies. Tumour-infiltrating lymphocytes (TILs) and monocytes/macrophages (TAMs) are proposed to have significance in cancer. However, there is only limited data concerning their impact on patient outcome and survival in hepatocellular carcinoma (HCC). Methods Frequencies of CD68 + , CD163 + M2-polarized TAMs and TILs were measured in de novo HCC tumours in non-cirrhosis ( n = 58) using immunohistology and correlated to patients’ clinicopathological characteristics and survival rates. Results Patients with tumours marked by appearance of TILs and CD68 + TAMs showed an improved 1-, 3- and 5-year recurrence-free survival (all p ≤ 0.05). CD68 + TAMs were associated with reduced incidence of recurrent and multifocal disease. Conversely, CD163 + TAMs were associated with multifocal HCC and lymphangiosis carcinomatosa (all p ≤ 0.05). Conclusions TILs and CD68 + TAMs are associated with multiple tumour characteristics and patient survival in HCC. However, there is only scarce data about the biology underlying their mechanistic involvement in human tumour progression. Thus, experimental data on functional links might help develop novel immunologic checkpoint inhibitor targets for liver cancer.

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“…Tumor-derived miRNAs induce polarization of anti-tumoral and pro-inflammatory M1 macrophages or Pro-tumoral and anti-inflammatory M2 macrophages. (108,109). TAMs mediate lung tumor progression enhanced by protein arginine methyl transferase 6 (PRMT6) (110).…”

Section: Exosomal Mirnas Of Tams Regulate Tumor Growth and Anti-cancementioning

confidence: 99%

Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages

Kwon

Kim

et al. 2020

Front. Immunol.

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Tumor microenvironment consists of cancer cells and various stromal cells such as endothelial cells, cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), neutrophils, macrophages, and other innate and adaptive immune cells. Of these innate immune cells, macrophages are an extremely heterogeneous population, and display both pro-inflammatory and anti-inflammatory functions. While M1 macrophages (classically activated macrophages) display anti-tumoral and pro-inflammatory functions, M2 macrophages display pro-tumoral and anti-inflammatory functions. Cellular interactions and molecular factors in the tumor microenvironment affect the polarization of macrophages. We review molecules and immune cells that influence the polarization status of macrophages. Tumor-associated macrophages (TAMs) generally express M2 phenotype, and mediate many processes that include tumor initiation, angiogenesis, and metastasis. A high number of TAMs has been associated with the poor prognosis of cancers. MicroRNAs (miRNAs) have been known to regulate cellular interactions that involve cancer cells and macrophages. Tumor-derived exosomes play critical roles in inducing the M1 or M2-like polarization of macrophages. The roles of exosomal miRNAs from tumor cells in the polarization of macrophages are also discussed and the targets of these miRNAs are presented. We review the effects of exosomal miRNAs from TAMs on cancer cell invasion, growth, and anti-cancer drug resistance. The relevance of exosomal microRNAs (miRNAs) as targets for the development of anti-cancer drugs is discussed. We review recent progress in the development of miRNA therapeutics aimed at elevating or decreasing levels of miRNAs.

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TIE2-expressing monocytes and M2-polarized macrophages impact survival and correlate with angiogenesis in adenocarcinoma of the pancreas

Cited by 40 publications

References 27 publications

Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

Immunologic cellular characteristics of the tumour microenvironment of hepatocellular carcinoma drive patient outcomes

Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages

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