Dataset Information

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice.

ABSTRACT: Tumor-associated macrophages (TAMs) as immune cells within the tumor microenvironment have gained much interests as basic science regarding their roles in tumor progression unfolds. Better understanding of their polarization into pro-tumoral phenotype to promote tumor growth, tumor angiogenesis, immune evasion, and tumor metastasis has prompted various studies to investigate their clinical significance as a biomarker of predictive and prognostic value across different cancer types. Yet, the methodologies to investigate the polarization phenomena in solid tumor tissue vary. Nonetheless, quantifying the ratio of M1 to M2 TAMs has emerged to be a prevailing parameter to evaluate this polarization phenomena for clinical application. This mini-review focuses on recent studies exploring clinical significance of M1/M2 TAM ratio in human cancer tissue and critically evaluates the technicalities and challenges in quantifying this parameter for routine clinical practice. Immunohistochemistry appears to be the preferred methodology for M1/M2 TAM evaluation as it is readily available in clinical laboratories, albeit with certain limitations. Recommendations are made to standardize the quantification of TAMs for better transition into clinical practice and for better comparison among studies in various populations of patients and cancer types.

SUBMITTER: Jayasingam SD

PROVIDER: S-EPMC6992653 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice.

Jayasingam Sharmilla Devi SD Citartan Marimuthu M Thang Thean Hock TH Mat Zin Anani Aila AA Ang Kai Cheen KC Ch'ng Ewe Seng ES

Frontiers in oncology 20200124

Tumor-associated macrophages (TAMs) as immune cells within the tumor microenvironment have gained much interests as basic science regarding their roles in tumor progression unfolds. Better understanding of their polarization into pro-tumoral phenotype to promote tumor growth, tumor angiogenesis, immune evasion, and tumor metastasis has prompted various studies to investigate their clinical significance as a biomarker of predictive and prognostic value across different cancer types. Yet, the meth ...[more]

PMID: 32039007

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Project description:A modified mesenchymal stem cell (MSC) transplantation is a highly effective and precise treatment for inflammatory bowel disease (IBD), with a significant curative effect. Thus, we aim to examine the efficacy of hypoxia-inducible factor (HIF)-1α-overexpressing MSC (HIF-MSC) transplantation in experimental colitis and investigate the immunity regulation mechanisms of HIF-MSC through macrophages. A chronic experimental colitis mouse model was established using 2,4,6-trinitrobenzene sulfonic acid. HIF-MSC transplantation significantly attenuated colitis in weight loss rate, disease activity index (DAI), colon length, and pathology score and effectively rebuilt the local and systemic immune balance. Macrophage depletion significantly impaired the benefits of HIF-MSCs on mice with colitis. Immunofluorescence analysis revealed that HIF-MSCs significantly decreased the number of M1-like macrophages and increased the number of M2-like macrophages in colon tissues. In vitro, co-culturing with HIF-MSCs significantly decreased the expression of pro-inflammatory factors, C-C chemokine receptor 7 (CCR-7), and inducible nitric oxide synthase (INOS) and increased the expression of anti-inflammatory factors and arginase I (Arg-1) in induced M1-like macrophages. Flow cytometry revealed that co-culturing with HIF-MSCs led to a decrease in the proportions of M1-like macrophages and an increase in that of M2-like macrophages. HIF-MSCs treatment notably upregulated the expression of downstream molecular targets of phosphatidylinositol 3-kinase-γ (PI3K-γ), including HIF-1α and p-AKT/AKT in the colon tissue. A selected PI3K-γ inhibitor, IPI549, attenuated these effects, as well as the effect on M2-like macrophage polarization and inflammatory cytokines in colitis mice. In vitro, HIF-MSCs notably upregulated the expression of C/EBPβ and AKT1/AKT2, and PI3K-γ inhibition blocked this effect. Modified MSCs stably overexpressed HIF-1α, which effectively regulated macrophage polarization through PI3K-γ. HIF-MSC transplantation may be a potentially effective precision therapy for IBD.

Dataset Information

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice.

Publications

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice.

Similar Datasets

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