Difference in distribution profiles between CD163+ tumor-associated macrophages and S100+ dendritic cells in thymic epithelial tumors

Omatsu, Mutsuko; Kunimura, Toshiaki; Mikogami, Tetsuya; Shiokawa, Akira; Nagai, Tomoko; Masunaga, Atsuko; Kitami, Akihiko; Suzuki, Takashi; Kadokura, Mitsutaka

doi:10.1186/s13000-014-0215-7

Cited by 9 publications

(16 citation statements)

References 34 publications

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“…From the perspective of immune microenvironment, innate immune cells such as DC and adaptive immune cells such as T cells played an important role in thymoma [ 13 , 42 , 43 ]. There was a strong correlation between LIPE and immune cells, suggesting that LIPE may participate in the prognosis of thymoma by regulating the immunity system.…”

Section: Discussionmentioning

confidence: 99%

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Identification of Molecular Characteristics and New Prognostic Targets for Thymoma by Multiomics Analysis

Liu

Zhang

Zhao

et al. 2021

BioMed Research International

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Background. Thymoma is a heterogeneous tumor originated from thymic epithelial cells. The molecular mechanism of thymoma remains unclear. Methods. The expression profile, methylation, and mutation data of thymoma were obtained from TCGA database. The coexpression network was constructed using the variance of gene expression through WGCNA. Enrichment analysis using clusterProfiler R package and overall survival (OS) analysis by Kaplan-Meier method were carried out for the intersection of differential expression genes (DEGs) screened by limma R package and important module genes. PPI network was constructed based on STRING database for genes with significant impact on survival. The impact of key genes on the prognosis of thymoma was evaluated by ROC curve and Cox regression model. Finally, the immune cell infiltration, methylation modification, and gene mutation were calculated. Results. We obtained eleven coexpression modules, and three of them were higher positively correlated with thymoma. DEGs in these three modules mainly involved in MAPK cascade and PPAR pathway. LIPE, MYH6, ACTG2, KLF4, SULT4A1, and TF were identified as key genes through the PPI network. AUC values of LIPE were the highest. Cox regression analysis showed that low expression of LIPE was a prognostic risk factor for thymoma. In addition, there was a high correlation between LIPE and T cells. Importantly, the expression of LIPE was modified by methylation. Among all the mutated genes, GTF2I had the highest mutation frequency. Conclusion. These results suggested that the molecular mechanism of thymoma may be related to immune inflammation. LIPE may be the key genes affecting prognosis of thymoma. Our findings will help to elucidate the pathogenesis and therapeutic targets of thymoma.

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Section: Discussionmentioning

confidence: 99%

“…In addition, the thymus provides a special microenvironment for the development and selection of mature T cells. Recent evidence suggests that immune responses such as T cells are involved in the development of thymoma [ 12 , 13 ]. However, the understanding of the pathogenesis of thymoma is still limited.…”

Section: Introductionmentioning

confidence: 99%

Identification of Molecular Characteristics and New Prognostic Targets for Thymoma by Multiomics Analysis

Liu

Zhang

Zhao

et al. 2021

BioMed Research International

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“…Thus, their phenotypic and functional integrity is a prerequisite for the occurrence of a de novo antigen-specific adaptive immune reaction. In TETs, mature dendritic cells’ immunophenotypic profile is characterized by Fascin and S100A expression, along with the absence of classic dendritic cells marker CD1a [ 25 , 26 ]. Immunohistochemical evaluation in resected thymus samples has revealed higher densities of such double-positive DCs in lower malignancy TETs subtypes, such as B1 and B2, while TCs are characterized by a scarcity of differentiated DCs [ 25 , 26 ].…”

Section: Immune Cell Populations Of Thymoma and Thymic Carcinomamentioning

confidence: 99%

Unraveling the Immune Microenvironment of Thymic Epithelial Tumors: Implications for Autoimmunity and Treatment

Masaoutis

Palamaris

Kokkali

et al. 2022

IJMS

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Thymic Epithelial Tumors (TETs) represent a rare tumor family, originating from the epithelial component of the thymus gland. Clinicopathologically, they are segregated into six major subtypes, associated with distinct histological features and clinical outcomes. Their emergence and evolution are accompanied by the generation of a complex tumor microenvironment (TME), dominated by phenotypically and functionally divergent immune cellular subsets, in different maturation states and in analogies that vary significantly among different subtypes. These heterogenous leukocyte populations exert either immune-permissive and tumor-suppressive functions or vice versa, and the dynamic equilibrium established among them either dictates the tumor immune milieu towards an immune-tolerance state or enables the development of a productive spontaneous tumoricidal response. The immunologically “hot” microenvironment, defining a significant proportion of TETs, makes them a promising candidate for the implementation of immune checkpoint inhibitors (ICIs). A number of phase I and II clinical trials have already demonstrated significant, type-specific clinical efficacy of PD-L1 inhibitors, even though substantial limitations in their utilization derive from their immune-mediated adverse effects. Moreover, the completed clinical studies involved relatively restricted patient samples and an expansion in the enrolled cohorts is required, so that more trustworthy conclusions regarding the benefit from ICIs in TETs can be extracted.

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“…Thus, CD163 is an ideal therapeutic target for drug delivery to Mϕ in both inflammatory disorders and cancers. [14][15][16] The physiological role of vitamin D 3 and its metabolite in calcium/phosphate homeostasis and bone metabolism has been elucidated. 17 Pre-vitamin D 3 is produced in the skin and transported by vitamin D-binding protein to the liver, where it is modified by Cyp27a1 into 25(OH)D 3 .…”

Section: Introductionmentioning

confidence: 99%

<p>Targeted lipid nanoparticle delivery of calcitriol to human monocyte-derived macrophages in vitro and in vivo: investigation of the anti-inflammatory effects of calcitriol</p>

Rafique¹,

Etzerodt²,

Graversen³

et al. 2019

IJN

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Background: Vitamin D 3 possesses anti-inflammatory and modulatory properties in addition to its role in calcium and phosphate homeostasis. Upon activation, macrophages (M) can initiate and sustain pro-inflammatory cytokine production in inflammatory disorders and play a pathogenic role in certain cancers. Purpose: The main purpose of this study was to encapsulate and specifically target calcitriol to macrophages and investigate the anti-inflammatory properties of calcitriol in vitro and in vivo. Methods: In this study we have designed and developed near-infrared calcitriol PEGylated nanoparticles (PEG-LNP(Cal)) using a microfluidic mixing technique and modified lipid nanoparticles (LNPs) to target the M specific endocytic receptor CD163. We have investigated LNP cellular uptake and anti-inflammatory effect in LPS-induced M in vitro by flow cytometry, confocal microscopy and gene expression analyses. LNP pharmacodynamics, bio-distribution and organ specific LNP accumulation was also investigated in mice in vivo. Results: In vitro, we observed the specific uptake of PEG-LNP(Cal)-hCD163 in human M, which was significantly higher than the non-specific uptake of control PEG-LNP(Cal)-IgG(h) in M. Pretreatment with encapsulated calcitriol was able to attenuate intracellular TNF-expression, and M surface marker HLA-DR expression more efficiently than free calcitriol in LPS-induced M in vitro. Encapsulated calcitriol diminished mRNA gene levels of TNF-, NF-B, MCP-1 and IL-6, while upregulating IL-10. TNF-and IL-6 protein secretion also decreased. In mice, an in vivo pharmacodynamic study of PEG-LNP(Cal) showed a rapid clearance of IgG and CD163 modified LNPs compared to PEG-LNP(Cal). Antibody modified PEG-LNP(Cal) accumulated in the liver, spleen and kidney, whereas unmodified PEG-LNP(Cal) accumulation was only observed in the liver. Conclusion: Our results show that calcitriol can be effectively targeted to M. Our data confirms the anti-inflammatory properties of calcitriol and this may be a potential way to deliver high dose bioactive calcitriol to M during inflammation in vivo.

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Difference in distribution profiles between CD163+ tumor-associated macrophages and S100+ dendritic cells in thymic epithelial tumors

Cited by 9 publications

References 34 publications

Identification of Molecular Characteristics and New Prognostic Targets for Thymoma by Multiomics Analysis

Identification of Molecular Characteristics and New Prognostic Targets for Thymoma by Multiomics Analysis

Unraveling the Immune Microenvironment of Thymic Epithelial Tumors: Implications for Autoimmunity and Treatment

<p>Targeted lipid nanoparticle delivery of calcitriol to human monocyte-derived macrophages in vitro and in vivo: investigation of the anti-inflammatory effects of calcitriol</p>

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