Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization

Huang, Cheng; Lewis, Curtis A.; Borg, Natalie A.; Canals, Meritxell; Diep, Henry; Drummond, Grant R; Goode, Robert J. A.; Schittenhelm, Ralf B.; Vinh, Antony; Zhu, Mingyu; Kemp-Harper, Barbara K; Kleifeld, Oded; Stone, Martin J.

doi:10.1021/acs.jproteome.7b00828

Cited by 43 publications

(39 citation statements)

References 66 publications

(115 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(2.7-fold) (12); while M2 markers included TGM2 (28-fold) (30) and CD209 (2.3-fold) (31). In addition, the over-expression of LSP1 (5-fold) was also detected in M2 type, which is consistent with a previous study (12).…”

Section: Polarization Of Human Thp-1 and Mouse Raw2647 Cell Lines Into M1 And M2 Macrophagessupporting

confidence: 90%

Comparative Proteomic Analysis of Polarized Human THP-1 and Mouse RAW264.7 Macrophages

Zou

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) in the immune system, performing pro-inflammatory and anti-inflammatory functions, respectively. Human THP-1 and mouse RAW264.7 cell line models have been widely used in various macrophage-associated studies, while the similarities and differences in protein expression profiles between the two macrophage models are still largely unclear. In this study, the protein expression profiles of M1 and M2 phenotypes from both THP-1 and RAW264.7 macrophages were systematically investigated using mass spectrometry-based proteomics. By quantitatively analyzing more than 5,000 proteins among different types of macrophages (M0, M1 and M2) from both cell lines, we identified a list of proteins that were uniquely up-regulated in each macrophage type and further confirmed 43 proteins that were commonly up-regulated in M1 macrophages of both cell lines. These results revealed considerable divergences of each polarization type between THP-1 and RAW264.7 macrophages. Moreover, the mRNA and protein expression of CMPK2, RSAD2, DDX58, and DHX58 were strongly up-regulated in M1 macrophages for both macrophage models. These data can serve as important resources for further studies of macrophage-associated diseases in experimental pathology using human and mouse cell line models.

show abstract

Section: Polarization Of Human Thp-1 and Mouse Raw2647 Cell Lines Into M1 And M2 Macrophagessupporting

confidence: 90%

Comparative Proteomic Analysis of Polarized Human THP-1 and Mouse RAW264.7 Macrophages

Zou

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…The rst subpopulation, C0_MHCII hi -CXCL2, characterised by Cxcl2, N l3 and Osm, had the phenotype of activated macrophages 38,39,40 . The second subpopulation showed signi cant expressions of I t3b, I t3 and I t2, typical of polarised M1 macrophages 41 , suggesting proin ammatory function. In addition, this subpopulation also showed signi cant upregulation of several other interferon-induced protein relevant genes, thus we labelled it as C1_MHCII hi -IFIT.…”

Section: Resultsmentioning

confidence: 95%

Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment

Ni¹,

Wu²,

Liu³

et al. 2020

Preprint

View full text Add to dashboard Cite

Development of a vaccine formula that alters the tumour-infiltrating lymphocytes to be more immune active against a tumour is key to the improvement of clinical responses to immunotherapy. Here, we demonstrate that, in conjunction with E7 antigen specific immunotherapy, and IL-10 and PD-1 blockade, intra-tumoral administration of caerin 1.1 and 1.9 peptides further improves the tumour microenvironment (TME) when compared with injection of a control peptide. We used single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity across different cell types within the TME. We show that the injection of caerin 1.1/1.9 increases immune activating macrophages and NK cells, while reducing immunosuppressive macrophages with M2 phenotype, and increased numbers of activated CD8+ T cells with higher populations of memory and effector-memory CD8+ T subsets. Proteomic profiling demonstrated activation of Stat1 modulated apoptosis and production of nitric oxide. Further, computational integration of the proteome with the single cell transcriptome was consistent with deactivation of immune suppressive B cell function following caerin 1.1 and 1.9 treatment.

show abstract

“…Further analysis using a Kaplan-Meier curve and Log-rank test revealed that all top 5 hub genes, except CCL5, influenced the RFS of patients with CRC. IRF1, which belongs to the IRF family (34), is weakly expressed in resting dendritic cells and macrophages, but is induced by interferon-γ (IFN-γ) in M1 polarized macrophages (35,36). Previous studies have revealed that IRF1 inhibited the proliferation and metastasis of CRC (37,38).…”

Section: Discussionmentioning

confidence: 99%

IRF1 association with tumor immune microenvironment and use as a diagnostic biomarker for colorectal cancer recurrence

Zhang

Yan

2020

Oncol Lett

View full text Add to dashboard Cite

Colorectal cancer (CRC) is considered to be one of the most lethal cancer types globally, and its recurrence is a major treatment challenge. Identifying the factors involved when determining the risk of CRC recurrence is required to improve personalized therapy for patients with CRC. Based on the GSE39582 dataset, the present study demonstrated that a higher ratio of M1 macrophages and activated memory CD4 + T cells indicated a better recurrence-free survival (RFS) time for CRC, using CIBERSORT and Pearson's correlation analysis. Through weighted correlation network analysis (WGCNA), an immune-associated module was identified that was significantly positively correlated with the ratio of M1 macrophages and activated memory CD4 + T cells. In this module, using WGCNA and a protein-protein interaction network, interferon regulatory factor 1 (IRF1), chemokine ligand 5, ubiquitin/ISG15-conjugating enzyme E2 L6, guanylate binding protein 1 and interleukin 2 receptor subunit beta were identified as hub genes. Among these genes, univariate Cox and multivariate Cox analysis revealed that IRF1 may be a potential diagnostic biomarker for RFS in patients with CRC. This was further validated using The Cancer Genome Atlas data. Gene set enrichment analysis demonstrated that IRF1 influenced the genes and pathways that are associated with immune cell recruitment and activation. Additionally, the DNA methylation of cg27587780 and cg15375424 CpG sites in the IRF1 gene region was indicated to be negatively correlated with IRF1 mRNA expression and positively correlated with the recurrence of CRC. Collectively, the results of the present study demonstrated that IRF1 may be a potential diagnostic biomarker for RFS in patients with CRC.

show abstract

Proteomic Identification of Interferon-Induced Proteins with Tetratricopeptide Repeats as Markers of M1 Macrophage Polarization

Cited by 43 publications

References 66 publications

Comparative Proteomic Analysis of Polarized Human THP-1 and Mouse RAW264.7 Macrophages

Comparative Proteomic Analysis of Polarized Human THP-1 and Mouse RAW264.7 Macrophages

Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment

IRF1 association with tumor immune microenvironment and use as a diagnostic biomarker for colorectal cancer recurrence

Contact Info

Product

Resources

About