High density of CD68+ tumor-associated macrophages predicts a poor prognosis in gastric cancer mediated by IL-6 expression

Su, Chongyu; Fu, Xiaolong; Duan, Wei; Yu, Ping; Zhao, Yongliang

doi:10.3892/ol.2018.8119

Cited by 25 publications

(26 citation statements)

References 21 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TAMs play a controversial role in tumor progression depending on different tumor types. TAMs infiltration has been shown to correlate with worse outcome in cancers, including breast cancer [36], oesophageal cancer [37], gastric cancer [38], and pancreatic cancer [39]. However, some studies indicated that TAMs were correlated with better prognosis in non-small cell lung cancer [40] and colorectal carcinoma [41].…”

Section: Discussionmentioning

confidence: 99%

Profiles of immune cell infiltration in head and neck squamous carcinoma

Liang

Wang

2020

Bioscience Reports

View full text Add to dashboard Cite

Tumor immune infiltration cells (TIICs) are highly heterogeneous, not only in different cancer subtypes but also within different cancer regions. We conducted the Cell-type Identification using Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) method. We assessed the relative proportions of 22 TIICs in HNSC using publicly available TCGA transcriptional datasets, analyzed the proportions of TIICs between HNSC tissues and normal tissues, along with accompanying clinicopathological data, and the impact of TIICs on clinical outcome. After the filter criteria, a total of 395 patients were included in the analysis. We found significant differences in naïve B cells, monocytes, resting mast cells, activated mast cells, CD8+ T cells, and M0 macrophages between HNSC tissues and adjacent non-cancer tissues. We also found that some TIIC subgroups were significantly associated with clinical parameters. Moreover, the patients with low Tregs fraction had worse OS and DFS than those with high Tregs fraction. However, low M0 macrophages fraction was associated with better OS and DFS in HNSC patients. Moreover, Tregs and M0 macrophages are likely to be important determinants of prognosis, which may serve as a potential immunotherapy target for HNSC. Then, we screened the immune-related differentially expressed genes (DEGs), performed the GO and KEGG enrichment analysis, constructed the protein–protein interaction network, and screened the prognosis-related hub genes in HNSC. However, further clinical investigation and basic experiments are needed to validate our results, and uncover the molecular mechanisms interlinking TIICs in HNSC and their roles in prognosis and therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Profiles of immune cell infiltration in head and neck squamous carcinoma

Liang

Wang

2020

Bioscience Reports

View full text Add to dashboard Cite

show abstract

“…IRF4 and histone demethylase Jumonji domains containing-3 (Jmjd3) are important players in IL-4-induced M2 polarization of macrophages acting through the activation of M2-specific genes (ARG1, FIZZ1, Ym1, and CD206) [31]. The level of IRF4 protein together with STAT3 and P-STAT3 proteins was elevated in monocyte-derived M2 macrophages induced by IL-6 in vitro [32]. ChIP assay demonstrated that IRF4 can be recruited to the PU.1 site and trans-activated by the MR enhancer reporter (pGL3-MR) in RAW264.7 cells, while transfection of macrophages with miR-125a suppressed IRF4 expression and pGL3-MR transactivation [93].…”

Section: Interferon Regulatory Factorsmentioning

confidence: 99%

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Larionova

Kazakova

Patysheva

et al. 2020

Cancers

View full text Add to dashboard Cite

Macrophages are key innate immune cells in the tumor microenvironment (TME) that regulate primary tumor growth, vascularization, metastatic spread and tumor response to various types of therapies. The present review highlights the mechanisms of macrophage programming in tumor microenvironments that act on the transcriptional, epigenetic and metabolic levels. We summarize the latest knowledge on the types of transcriptional factors and epigenetic enzymes that control the direction of macrophage functional polarization and their pro- and anti-tumor activities. We also focus on the major types of metabolic programs of macrophages (glycolysis and fatty acid oxidation), and their interaction with cancer cells and complex TME. We have discussed how the regulation of macrophage polarization on the transcriptional, epigenetic and metabolic levels can be used for the efficient therapeutic manipulation of macrophage functions in cancer.

show abstract

“…There are recent reports of tumors being infiltrated by macrophages that possess proangiogenic activity, and that are generally associated with high vascular density [ 3 ]. Increased infiltration of tumor-associated macrophages (TAMs) has also been associated with worsening pathologic characteristics and a poor prognosis in breast, colon, and bladder cancer [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of let-7b-5p contributes to an anti-tumorigenic macrophage phenotype through the SOCS1/STAT pathway in prostate cancer

Rong

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background Dysfunction of microRNAs (miRNAs) is a major cause of aberrant expression of inflammatory cytokines and contributes to macrophage polarization. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity, whereas M2 macrophages display regulatory functions in tissue repair and remodeling and promote Th2 immune responses. Previous studies have shown that miRNA let-7 is associated with cellular differentiation and that the expression of let-7b-5p is significantly augmented in M2 macrophages. However, the mechanism by which let-7b-5p regulates macrophage differentiation in prostate cancer (PCa) remains largely unknown. Methods Human macrophages were induced by blood monocytes from healthy male donors, and M1 macrophages were polarized by stimulating them overnight with 100 ng/ml of lipopolysaccharides and 100 ng/ml of IFN-γ. Conditioned medium from PC-3 cells was used to induce prostatic macrophages (M-CMs) in vitro, and we then transfected let-7b-5p mimics or inhibitors into M1 and M-CMs for 72 h. The expression of cluster of differentiation 206 (CD206) in each group was detected with the High-Throughput Connotation of Imaging System. We used quantitative real-time polymerase chain reaction (qRT-PCR) to examine the expression of the inflammatory cytokines IL-10, IL-12, IL-13, TNF-alpha, and let-7b in macrophages. SOCS1 protein levels were evaluated by ELISA, and the phosphorylation difference in STAT family member proteins was analyzed using CST signal-pathway chip. Phagocytosis by macrophages and the effect of macrophages on the proliferation of prostate cancer PC-3 cells were evaluated with phagocytosis assay or the Cell Counting Kit-8 (CCK-8) and colony formation assay. The relationship between SOCS1 and let-7b-5p was confirmed with a dual-luciferase reporter. Results The expression of cluster of differentiation 206 (CD206, a M2-like macrophage surface molecule) was significantly increased in M1 macrophages treated with let-7b-5p mimics, while CD206 expression was decreased in M-CMs treated with let-7b-5p inhibitors. Overexpression or knockdown of let-7b-5p significantly affected the expression of inflammatory factors in macrophages—including interleukin 10 (IL-10), IL-12, IL-13, and tumor necrosis factor alpha. Let-7b-5p downregulated the expression of suppressor of cytokine signaling 1 (SOCS1) and increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5a proteins in M-CMs and M1 macrophages with let-7b-5p mimics relative to the other groups. In addition, with the elevated expression of let-7b-5p, the phagocytosis by macrophages showed a commensurate and significant decrease. As a result, M-CMs treated with let-7b-5p inhibitors reduced the proliferation of PC-3 PCa cells. Conclusions Collectively, these data indicated that let-7b-5p may regulate M2 polarization through the SOCS1/STAT pathway and that reversal of M2 differentiation by let-7b-5p inhibitors enhanced macrophage phagocytosis, ultimately inhibiting the proliferation of PCa cells.

show abstract

High density of CD68+ tumor-associated macrophages predicts a poor prognosis in gastric cancer mediated by IL-6 expression

Cited by 25 publications

References 21 publications

Profiles of immune cell infiltration in head and neck squamous carcinoma

Profiles of immune cell infiltration in head and neck squamous carcinoma

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Inhibition of let-7b-5p contributes to an anti-tumorigenic macrophage phenotype through the SOCS1/STAT pathway in prostate cancer

Contact Info

Product

Resources

About