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Macrophage Repolarization as a Therapeutic Strategy for Osteosarcoma.

ABSTRACT: Macrophages are versatile immune cells and can adapt to both external stimuli and their surrounding environment. Macrophages are categorized into two major categories; M1 macrophages release pro-inflammatory cytokines and produce protective responses that lead to antimicrobial or antitumor activity. M2 or tumor-associated macrophages (TAM) release anti-inflammatory cytokines that support tumor growth, invasion capacity, and metastatic potential. Since macrophages can be re-polarized from an M2 to an M1 phenotype with a variety of strategies, this has emerged as an innovative anti-cancer approach. Osteosarcoma (OS) is a kind of bone cancer and consists of a complex niche, and immunotherapy is not very effective. Therefore, immediate attention to new strategies is required. We incorporated the recent studies that have used M2-M1 repolarization strategies in the aspect of treating OS cancer.

SUBMITTER: Anand N

PROVIDER: S-EPMC9917837 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Macrophage Repolarization as a Therapeutic Strategy for Osteosarcoma.

Anand Namrata N Peh Keng Hee KH Kolesar Jill M JM

International journal of molecular sciences 20230202 3

Macrophages are versatile immune cells and can adapt to both external stimuli and their surrounding environment. Macrophages are categorized into two major categories; M1 macrophages release pro-inflammatory cytokines and produce protective responses that lead to antimicrobial or antitumor activity. M2 or tumor-associated macrophages (TAM) release anti-inflammatory cytokines that support tumor growth, invasion capacity, and metastatic potential. Since macrophages can be re-polarized from an M2 t ...[more]

PMID: 36769180

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Project description:BackgroundMacrophage plasticity allows cells to adopt different phenotypes, a property with important implications in disorders such as cystic fibrosis (CF) and asthma.ObjectiveWe sought to examine the transcriptional and functional significance of macrophage repolarization from an M1 to an M2 phenotype and assess the role of a common human genetic disorder (CF) and a prototypical allergic disease (asthma) in this transformation.MethodsMonocyte-derived macrophages were collected from healthy subjects and patients with CF and polarized to an M2 state by using IL-4, IL-10, glucocorticoids, apoptotic PMNs, or azithromycin. We performed transcriptional profiling and pathway analysis for each stimulus. We assessed the ability of M2-repolarized macrophages to respond to LPS rechallenge and clear apoptotic neutrophils and used murine models to determine conserved functional responses to IL-4 and IL-10. We investigated whether M2 signatures were associated with alveolar macrophage phenotypes in asthmatic patients.ResultsWe found that macrophages exhibit highly diverse responses to distinct M2-polarizing stimuli. Specifically, IL-10 activated proinflammatory pathways and abrogated LPS tolerance, allowing rapid restoration of LPS responsiveness. In contrast, IL-4 enhanced LPS tolerance, dampening proinflammatory responses after repeat LPS challenge. A common theme observed across all M2 stimuli was suppression of interferon-associated pathways. We found that CF macrophages had intact reparative and transcriptional responses, suggesting that macrophage contributions to CF-related lung disease are primarily shaped by their environment. Finally, we leveraged in vitro-derived signatures to show that allergen provocation induces distinct M2 state transcriptional patterns in alveolar macrophages.ConclusionOur findings highlight the diversity of macrophage polarization, attribute functional consequences to different M2 stimuli, and provide a framework to phenotype macrophages in disease states.

Dataset Information

Macrophage Repolarization as a Therapeutic Strategy for Osteosarcoma.

Publications

Macrophage Repolarization as a Therapeutic Strategy for Osteosarcoma.

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