IFN regulatory factor–8 expression in macrophages governs an antimetastatic program

Twum, Danielle Y. F.; Colligan, Sean; Hoffend, Nicholas C.; Katsuta, Eriko; Gomez, Eduardo Cortes; Hensen, Mary L.; Seshadri, Mukund; Nemeth, Michael J.; Abrams, Scott I.

doi:10.1172/jci.insight.124267

“…Decreased metastasis and increased survival in human breast, lung cancers and melanoma. Associated with prolonged DFS in RCC patient [18,36,37] KLF4…”

Section: Transcription Regulation Of Macrophage Polarizationmentioning

confidence: 99%

“…Inhibition of IRF8 in macrophages reduces expression of inflammatory mediators associated with M1 macrophage (IL-1b, IL-6, iNOS, and TNF-α) and delayed wound healing in vivo [97]. IRF8 deficiency in macrophages significantly increased metastasis and expression of metastatic-associated genes in the mouse models of mammary cancer and melanoma, and correlated with reduced survival in human breast and lung cancers and melanoma [36]. High levels of IRF8 expression is associated with prolonged DFS in renal cell carcinoma patients [37].…”

Section: Interferon Regulatory Factorsmentioning

confidence: 99%

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Larionova

¹

,

Kazakova

²

,

Patysheva

³

et al. 2020

Cancers

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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.

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“…regulates the development and function of a variety of immune cells, linking innate and adaptive immunity [21] . It plays a regulatory role in the cell's immune response to cancer and can mediate the expression of Fas, Bax, JAK, and STAT, leading to the apoptosis of solid tumor cells and has been shown to have antitumor activity in a variety of tumor cells [22] .…”

Section: Discussionmentioning

confidence: 99%

Identification of key prognosis-associated genes in the lung adenocarcinoma

Ma

¹

,

Wu

²

,

Tao

³

et al. 2020

Preprint

0

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Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer-related death globally, and lung adenocarcinoma (LUAD) accounts for almost 40% of all lung cancer cases. In recent years, despite better understanding of the pathogenesis of the disease and achievements in the multimodal treatment of tumors, there is an urgent need to identify new diagnostic and prognostic biomarkers In this study, we aim to identify the potential key genes related to the pathogenesis and prognosis of LUAD by using comprehensive bioinformatics analysis. The gene expression profile was downloaded from The Cancer Genome Atlas (TCGA) database, and we calculated the LUAD immune scores and stromal scores by using the ESTIMATE algorithm. Based on these scores, we further quantified the immune and stromal components and obtained the differentially expressed genes (DEGs) in the tumor. Overall survival analysis could better reflect the impact of genes related to immune and stromal cells on the prognosis. Moreover, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted, while protein-protein interaction (PPI) network was obtained from STRING. Analysis of the correlation revealed that these genes are mainly involved in the immune/inflammatory response. In conclusion, our study showed that 11 prognostic genes (CD33, IRF8, CD80, CD53, IL16, LY86, CD79B, TYROBP, CD1E, CD1C, and CD1B) might show a potentially good performance in predicting overall survival in patients with LUAD. In summary, we identified the key genes related to the microenvironment, which can further serve as the prognostic biomarkers and therapeutic targets for LUAD.

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“…IRF8, Interferon regulatory factor 8, is a member of the IRF family of transcription factors. IRF8 regulates the development and function of a variety of immune cells, linking innate and adaptive immunity [21] . It plays a regulatory role in the cell's immune response to cancer and can mediate the expression of Fas, Bax, JAK, and STAT, leading to the apoptosis of solid tumor cells and has been shown to have antitumor activity in a variety of tumor cells [22] .…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Prognosis-Associated Genes in the Lung Adenocarcinoma

Ma

¹

,

Wu

²

,

Tao

³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer-related death globally, and lung adenocarcinoma (LUAD) accounts for almost 40% of all lung cancer cases. In recent years, despite better understanding of the pathogenesis of the disease and achievements in the multimodal treatment of tumors, there is an urgent need to identify new diagnostic and prognostic biomarkers In this study, we aim to identify the potential key genes related to the pathogenesis and prognosis of LUAD by using comprehensive bioinformatics analysis. The gene expression profile was downloaded from The Cancer Genome Atlas (TCGA) database, and we calculated the LUAD immune scores and stromal scores by using the ESTIMATE algorithm. Based on these scores, we further quantified the immune and stromal components and obtained the differentially expressed genes (DEGs) in the tumor. Overall survival analysis could better reflect the impact of genes related to immune and stromal cells on the prognosis. Moreover, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted, while protein-protein interaction (PPI) network was obtained from STRING. Analysis of the correlation revealed that these genes are mainly involved in the immune/inflammatory response. In conclusion, our study showed that 11 prognostic genes (CD33, IRF8, CD80, CD53, IL16, LY86, CD79B, TYROBP, CD1E, CD1C, and CD1B) might show a potentially good performance in predicting overall survival in patients with LUAD. In summary, we identified the key genes related to the microenvironment, which can further serve as the prognostic biomarkers and therapeutic targets for LUAD.

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IFN regulatory factor–8 expression in macrophages governs an antimetastatic program

Cited by 27 publications

References 62 publications

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Identification of key prognosis-associated genes in the lung adenocarcinoma

Identification of Key Prognosis-Associated Genes in the Lung Adenocarcinoma

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