Mathematical investigation of innate immune responses to lung cancer: The role of macrophages with mixed phenotypes

Eftimie, Raluca; Barelle, Charlotte

doi:10.1016/j.jtbi.2021.110739

Cited by 25 publications

(26 citation statements)

References 45 publications

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“…influenced by the half-life of various macrophage phenotypes (43). The abundance of these macrophages indicates the plasticity of TAMs and the potential of targeting TAMs for immunotherapy in medulloblastoma.…”

Section: Discussionmentioning

confidence: 99%

“…We did not find any correlation between M mix and prognosis in this study. A recent research showed that tumor reduction was associated with the percentage of macrophages with mixed M1/M2 phenotypes, and the outcome of these therapeutic strategies targeting TAMs was influenced by the half-life of various macrophage phenotypes ( 43 ). The abundance of these macrophages indicates the plasticity of TAMs and the potential of targeting TAMs for immunotherapy in medulloblastoma.…”

Section: Discussionmentioning

confidence: 99%

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Tumor-Associated Macrophages Correlate With Prognosis in Medulloblastoma

et al. 2022

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PurposeMacrophage polarization plays an essential role in the tumor microenvironment of brain tumors. However, the role of tumor-associated macrophages (TAMs) in medulloblastoma still remains controversial. Thus, we investigated the distribution of macrophages in medulloblastoma tissues and analyzed the association of TAM recruitment and medulloblastoma patients’ outcomes.MethodsWe obtained a total of 71 paraffin sections from patients with medulloblastoma, and detected the activated phenotype (M1/M2) by monoclonal antibodies for CD68, HLA-DR and CD163 with multiple fluorescence immunohistochemistry method. The number of polarized macrophages was quantified using the InForm software. Outcomes were analyzed according to clinical data and quantified macrophage data.ResultsThe study revealed that TAMs were significantly higher in sonic hedgehog (SHH) medulloblastoma than in other subgroups, and M1 macrophages in metastatic group were significantly higher than those in non-metastatic group. A Kaplan-Meier survival analysis and multivariate Cox regression model showed the correlation of high percentage of total macrophages (P = 0.038, HR = 0.241) and M1 macrophages (P = 0.034, HR = 0.333) with good 5-year progression-free survival (PFS); however, M2 macrophages had no correlation with survival of medulloblastoma patients (P> 0.05).ConclusionHigh percentage of total macrophages and M1 macrophages are correlated with good outcome of medulloblastoma patients. TAMs might be a target of therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tumor-Associated Macrophages Correlate With Prognosis in Medulloblastoma

et al. 2022

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“…Recent studies have shown that the interaction between macrophages and Treg through ligand receptor interaction may contribute to immunosuppressive status and disease progression (32). Macrophages are the main components of the immune infiltrate of the tumor microenvironment and can produce a variety of phenotypes in different microenvironments, including classically activated (M1) and alternately activated (M2) macrophages (33). M1-like cells are involved in pathogen clearance and proinflammatory responses, and M2-like cells promote tissue remodeling and anti-inflammatory processes and are related to tumor progression (15) that infiltrate tumor tissues, called tumor-associated macrophages, are associated with tumor progression and metastasis.…”

Section: Discussionmentioning

confidence: 99%

The role of miR-145-5p in esophageal squamous cell carcinoma tumor-associated macrophages and selection of immunochemotherapy

Lin¹,

Wu²,

Zhu³

et al. 2022

J Thorac Dis

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Background The impact of miR-145-5p in immune infiltration and the potential application in esophageal squamous cell carcinoma (ESCC) immunochemotherapy remains unknown. Methods Transcriptomic data for ESCC tissues and normal tissues and clinical materials of patients with ESCC were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differences in mRNA levels in cancer tissues and noncancerous tissues were analyzed, and we subsequently investigated the association between miR-145-5p expression and the key parameters of ESCC progression and prognosis. Additionally, cytological experiments were performed to evaluate the biological functions of miR-145-5p. Pathways potentially affected by miR-145-5p were analyzed by Gene Set Enrichment Analysis (GSEA) and REACTOME. We also analyzed the function of miR-145-5p in immune infiltration through the TIMER2 (Tumor Immune Estimation Resource) database. Results The analysis of gene chip data from the TCGA database and GEO database (including GSE13937 and GSE43732) showed that the expression of miR-145-5p is downregulated in ESCC (P<0.05) and that patients with high miR-145-5p levels had lower survival rates (P<0.05). The expression of miR-145-5p was significantly correlated with the disease-free survival (DFS) rate (P<0.05) and M stage (P<0.05) in the TCGA database and was significantly correlated with the T stage (P<0.05) and TNM stage (P<0.05) in the GSE13937 database. Functional experiments showed that miR-145-5p attenuated proliferation (P<0.05), migration (P<0.01) and invasion (P<0.01) in the Eca109 cell line. Both GSEA gene enrichment and REACTOME gene enrichment revealed that miR-145-5p was associated with tumor signaling pathways and immune signaling pathways. Immune infiltration analysis revealed that the expression level of miR-145-5p was significantly correlated with the infiltration level of macrophages (P<0.05) and was positively correlated with the level of gene markers of M2 macrophages and tumor-associated macrophages (P<0.05). Conclusions MiR-145-5p acts as a tumor suppressor microRNA in ESCC and is an important noncoding RNA in the high M2-like tumor-associated macrophage infiltration of ESCC. Assessing the miR-145-5p level in ESCC samples has translational meaning, which help illustrate the immune infiltration status, predict the prognostic outcome, and select the type of immunochemotherapy.

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“…Mathematical model has become a powerful, simple and economical tool to quantitatively study the potential mechanism of biological system in recent decades. It is noticed that some literatures have established corresponding mathematical models to describe the dynamical behavior of tumor and macrophages [6,7,8,1,37,9]. R. Eftimie [7] established a three-dimensional mathematical model of tumors, M1 macrophages and M2 macrophages, in which the logistic term describes the self proliferation and recruitment of macrophages.…”

mentioning

confidence: 99%

“…R. Eftimie [7] established a three-dimensional mathematical model of tumors, M1 macrophages and M2 macrophages, in which the logistic term describes the self proliferation and recruitment of macrophages. Raluca Eftimie and Charlotte Barelle [8] took into account the mixed phenotypes macrophages M12 in the tumor microenvironment, and established a four-dimensional mathematical model. Because monocyte input is less and recruitment is ignored, the logistic term in the model only describes the proliferation of macrophages.…”

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confidence: 99%

Mathematical investigation of the role of re-polarisation of M2 in cancer therapy

Guo

Fan

Wang

2023

DCDS-B

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<p style='text-indent:20px;'>Tumor-associated macrophages are one of the important immune cells in tumor microenvironment and they have both anti-tumor and pro-tumor roles as determined by their phenotypes. Recent experiments have shown that repolarizing pro-tumor M2 into anti-tumor M1 is a feasible antitumor therapy. Here we propose a mathematical model for the tumor-macrophage interactions with M2 re-polarisation delay to investigate the effect of M2 re-polarisation on tumor growth/decay. By using stability and bifurcation theories of DDE, we study the dynamic of this model analytically and numerically and find that the varies of M2 re-polarisation rate and time delay can cause complex dynamical behaviors such as the changes of stabilities of tumor-free, large and small tumor equilibria, the occurrences of saddle-node, Hopf, homoclinic and B-T bifurcation, etc. Moreover, our study reveals that the increase of M2 re-polarisation rate related to immunotherapeutic agent dose can control the tumor to small tumor dormancy and even eliminate the tumor, but this is not always available when immune escape occurs; Pharmacodynamic delay (M2 re-polarisation delay) also affects tumor progression and may cause persistent oscillatory behavior. In addition, the results also indicate the possibility of pseudo-progression in tumor therapy and efficacy of postoperative M2 re-polarisation therapy to prevent tumor recurrence.</p>

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Mathematical investigation of innate immune responses to lung cancer: The role of macrophages with mixed phenotypes

Cited by 25 publications

References 45 publications

Tumor-Associated Macrophages Correlate With Prognosis in Medulloblastoma

Tumor-Associated Macrophages Correlate With Prognosis in Medulloblastoma

The role of miR-145-5p in esophageal squamous cell carcinoma tumor-associated macrophages and selection of immunochemotherapy

Mathematical investigation of the role of re-polarisation of M2 in cancer therapy

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