Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TYROBP, TLR4 and ITGAM regulated macrophages polarization and immune checkpoints expression in osteosarcoma.

ABSTRACT: We established a relationship among the immune-related genes, tumor-infiltrating immune cells (TIICs), and immune checkpoints in patients with osteosarcoma. The gene expression data for osteosarcoma were downloaded from UCSC Xena and GEO database. Immune-related differentially expressed genes (DEGs) were detected to calculate the risk score. "Estimate" was used for immune infiltrating estimation and "xCell" was used to obtain 64 immune cell subtypes. Furthermore, the relationship among the risk scores, immune cell subtypes, and immune checkpoints was evaluated. The three immune-related genes (TYROBP, TLR4, and ITGAM) were selected to establish a risk scoring system based on their integrated prognostic relevance. The GSEA results for the Hallmark and KEGG pathways revealed that the low-risk score group exhibited the most gene sets that were related to immune-related pathways. The risk score significantly correlated with the xCell score of macrophages, M1 macrophages, and M2 macrophages, which significantly affected the prognosis of osteosarcoma. Thus, patients with low-risk scores showed better results with the immune checkpoints inhibitor therapy. A three immune-related, gene-based risk model can regulate macrophage activation and predict the treatment outcomes the survival rate in osteosarcoma.

SUBMITTER: Liang T

PROVIDER: S-EPMC8481262 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Profiling targetable immune checkpoints in osteosarcoma.

Project description:Osteosarcomas are aggressive bone tumors for which therapeutic advances have not improved over several decades. Unlike most pediatric tumors, the osteosarcoma genome is remarkably unstable, characterized by numerous copy number alterations and chromosomal structural aberrations. In this study, we asked if the targetable immune checkpoints CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3) and IDO1 are impacted by copy number alterations in osteosarcoma. Of the 215 osteosarcoma samples investigated, PD-L1/PD-L2, B7-H3 and IDO1 were independently gained at frequencies of approximately 8-9%, with a cumulative frequency of approximately 24%. RNA sequencing data from two independent cohorts revealed that B7-H3 is the most highly expressed immune checkpoint gene among the four investigated. We also show that IDO1 is preferentially expressed in pediatric solid tumors and that increased protein expression of B7-H3 and IDO1 are significantly associated with inferior survival in patient samples. Using human osteosarcoma cell lines, we demonstrate that IDO1 is gained in MG63 and G292 cells and that the IDO1 inhibitor, epacadostat, inhibits the enzymatic activity of IDO1 in a dose-dependent manner in these cells. Together, these data reveal the genomic and transcriptomic profiles of PD-L1, PD-L2, B7-H3 and IDO1 in osteosarcoma and identifies a potential context for targeted immunotherapeutic intervention in a subset of patients.

| S-EPMC6279416 | biostudies-literature

A TLR4 Agonist Induces Osteosarcoma Regression by Inducing an Antitumor Immune Response and Reprogramming M2 Macrophages to M1 Macrophages.

Project description:Osteosarcoma (OsA) has limited treatment options and stagnant 5-year survival rates. Its immune microenvironment is characterized by a predominance of tumor-associated macrophages (TAMs), whose role in OsA progression remain unclear. Nevertheless, immunotherapies aiming to modulate macrophages activation and polarization could be of interest for OsA treatment. In this study, the antitumor effect of a liposome-encapsulated chemically detoxified lipopolysaccharide (Lipo-MP-LPS) was evaluated as a therapeutic approach for OsA. Lipo-MP-LPS is a toll-like receptor 4 (TLR4) agonist sufficiently safe and soluble to be IV administered at effective doses. Lipo-MP-LPS exhibited a significant antitumor response, with tumor regression in 50% of treated animals and delayed tumor progression in the remaining 50%. The agent inhibited tumor growth by 75%, surpassing the efficacy of other immunotherapies tested in OsA. Lipo-MP-LPS modulated OsA's immune microenvironment by favoring the transition of M2 macrophages to M1 phenotype, creating a proinflammatory milieu and facilitating T-cell recruitment and antitumor immune response. Overall, the study demonstrates the potent antitumor effect of Lipo-MP-LPS as monotherapy in an OsA immunocompetent model. Reprogramming macrophages and altering the immune microenvironment likely contribute to the observed tumor control. These findings support the concept of immunomodulatory approaches for the treatment of highly resistant tumors like OsA.

| S-EPMC10526955 | biostudies-literature

Prognostic significance and therapeutic potentials of immune checkpoints in osteosarcoma.

Project description:Although there exist manifold strategies for cancer treatment, researchers are obliged to develop novel treatments based on the challenges that arise. One of these recent treatment approaches is cancer immunotherapy, which enjoys various types of strategies itself. However, one of the most significant methods, in this regard, is employing immune checkpoint proteins (ICPs). Bone sarcomas have several subtypes, with the most common ones being chordoma, chondrosarcoma, Ewing sarcoma, and osteosarcoma. Although many aggressive treatment approaches, including radiotherapy, chemotherapy, and surgical resection, have been employed over the last decades, significantly improved outcomes have not been observed for Ewing sarcoma or osteosarcoma patients. Additionally, chordoma and chdrosarcoma resist against both radiation and chemotherapy. Accordingly, elucidating how recent therapies could affect bone sarcomas is necessary. Checkpoint inhibitors have attracted great attention for the treatment of several cancer types, including bone sarcoma. Herein, the recent advances of current immune checkpoint targets, such as anti-PD-1/PD-L1 and anti-CTLA-4 blockade, for the treatment of bone sarcoma have been reviewed.

| S-EPMC8822307 | biostudies-literature

Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy.

Project description:Unprecedented breakthroughs have been made in cancer immunotherapy in recent years. Particularly immune checkpoint inhibitors have fostered hope for patients with cancer. However, immunotherapy still exhibits certain limitations, such as a low response rate, limited efficacy in certain populations, and adverse events in certain tumors. Therefore, exploring strategies that can improve clinical response rates in patients is crucial. Tumor-associated macrophages (TAMs) are the predominant immune cells that infiltrate the tumor microenvironment and express a variety of immune checkpoints that impact immune functions. Mounting evidence indicates that immune checkpoints in TAMs are closely associated with the prognosis of patients with tumors receiving immunotherapy. This review centers on the regulatory mechanisms governing immune checkpoint expression in macrophages and strategies aimed at improving immune checkpoint therapies. Our review provides insights into potential therapeutic targets to improve the efficacy of immune checkpoint blockade and key clues to developing novel tumor immunotherapies.

| S-EPMC10258331 | biostudies-literature

Macrophages in Osteosarcoma Immune Microenvironment: Implications for Immunotherapy.

Project description:Osteosarcoma is a malignant primary bone tumor commonly occurring in children and adolescents. The treatment of local osteosarcoma is mainly based on surgical resection and chemotherapy, whereas the improvement of overall survival remains stagnant, especially in recurrent or metastatic cases. Tumor microenvironment (TME) is closely related to the occurrence and development of tumors, and macrophages are among the most abundant immune cells in the TME. Due to their vital roles in tumor progression, macrophages have gained increasing attention as the new target of tumor immunotherapy. In this review, we present a brief overview of macrophages in the TME and highlight the clinical significance of macrophages and their roles in the initiation and progression of osteosarcoma. Finally, we summarize the therapeutic approaches targeting macrophage, which represent a promising strategy in osteosarcoma therapies.

| S-EPMC7758531 | biostudies-literature

Lanosterol Modulates TLR4-Mediated Innate Immune Responses in Macrophages.

Project description:Macrophages perform critical functions in both innate immunity and cholesterol metabolism. Here, we report that activation of Toll-like receptor 4 (TLR4) in macrophages causes lanosterol, the first sterol intermediate in the cholesterol biosynthetic pathway, to accumulate. This effect is due to type I interferon (IFN)-dependent histone deacetylase 1 (HDAC1) transcriptional repression of lanosterol-14α-demethylase, the gene product of Cyp51A1. Lanosterol accumulation in macrophages, because of either treatment with ketoconazole or induced conditional disruption of Cyp51A1 in mouse macrophages in vitro, decreases IFNβ-mediated signal transducer and activator of transcription (STAT)1-STAT2 activation and IFNβ-stimulated gene expression. These effects translate into increased survival to endotoxemic shock by reducing cytokine secretion. In addition, lanosterol accumulation increases membrane fluidity and ROS production, thus potentiating phagocytosis and the ability to kill bacteria. This improves resistance of mice to Listeria monocytogenes infection by increasing bacterial clearance in the spleen and liver. Overall, our data indicate that lanosterol is an endogenous selective regulator of macrophage immunity.

| S-EPMC5553565 | biostudies-literature

The role of SPI1-TYROBP-FCER1G network in oncogenesis and prognosis of osteosarcoma, and its association with immune infiltration.

Project description:Osteosarcoma is an aggressive malignant bone sarcoma worldwide. A causal gene network with specific functions underlying both the development and progression of OS was still unclear. Here we firstly identified the differentially expressed genes (DEGs) between control and OS samples, and then defined the hub genes and top clusters in the protein-protein interaction (PPI) network of these DEGs. By focusing on the hub gene TYROBP in the top 1 cluster, a conserved TYROBP co-expression network was identified. Then the effect of the network on OS overall survival was analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and Gene Set Enrichment Analysis (GSEA) were used to explore the functions of the network. XCell platform and ssGSEA algorithm were conducted to estimate the status of immune infiltration. ChEA3 platform, GSEA enrichment analysis, and Drug Pair Seeker (DPS) were used to predict the key transcription factor and its upstream signal. We identified the downregulated SPI1-TYROBP-FCER1G network in OS, which were significantly enriched in immune-related functions. We also defined a two-gene signature (SPI1/FCER1G) that can predict poorer OS overall survival and the attenuated immune infiltration when downregulated. The SPI1-TYROBP-FCER1G network were potentially initiated by transcription factor SPI1 and would lead to the upregulated CD86, MHC-II, CCL4/CXCL10/CX3CL1 and hence increased immune infiltrations. With this study, we could better explore the mechanism of OS oncogenesis and metastasis for developing new therapies.

| S-EPMC8790913 | biostudies-literature

Immune Checkpoints Expression in Chronic Lung Allograft Rejection.

Project description:Chronic lung allograft dysfunction (CLAD) is the main cause of poor survival and low quality of life of lung transplanted patients. Several studies have addressed the role of dendritic cells, macrophages, T cells, donor specific as well as anti-HLA antibodies, and interleukins in CLAD, but the expression and function of immune checkpoint molecules has not yet been analyzed, especially in the two CLAD subtypes: BOS (bronchiolitis obliterans syndrome) and RAS (restrictive allograft syndrome). To shed light on this topic, we conducted an observational study on eight consecutive grafts explanted from patients who received lung re-transplantation for CLAD. The expression of a panel of immune molecules (PD1/CD279, PDL1/CD274, CTLA4/CD152, CD4, CD8, hFoxp3, TIGIT, TOX, B-Cell-Specific Activator Protein) was analyzed by immunohistochemistry in these grafts and in six control lungs. Results showed that RAS compared to BOS grafts were characterized by 1) the inversion of the CD4/CD8 ratio; 2) a higher percentage of T lymphocytes expressing the PD-1, PD-L1, and CTLA4 checkpoint molecules; and 3) a significant reduction of exhausted PD-1-expressing T lymphocytes (PD-1pos/TOXpos) and of exhausted Treg (PD-1pos/FOXP3pos) T lymphocytes. Results herein, although being based on a limited number of cases, suggest a role for checkpoint molecules in the development of graft rejection and offer a possible immunological explanation for the worst prognosis of RAS. Our data, which will need to be validated in ampler cohorts of patients, raise the possibility that the evaluation of immune checkpoints during follow-up offers a prognostic advantage in monitoring the onset of rejection, and suggest that the use of compounds that modulate the function of checkpoint molecules could be evaluated in the management of chronic rejection in LTx patients.

| S-EPMC8418069 | biostudies-literature

Expression patterns of immune checkpoints in acute myeloid leukemia.

Project description:Immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival. This type of therapy is still not available for acute myeloid leukemia (AML). One major issue is the lack of knowledge for the expression patterns of immune checkpoints (IC) in AML. In this study, we first explored the prognostic value of ICs for AML patients by analyzing RNA-seq and mutation data from 176 AML patients from the Cancer Genome Atlas (TCGA) database. We further validated the results of the database analysis by analyzing bone marrow (BM) samples from 62 patients with de novo AML. Both TCGA data and validation results indicated that high expression of PD-1, PD-L1, and PD-L2 was associated with poor overall survival (OS) in AML patients. In addition, increased co-expression of PD-1/CTLA-4 or PD-L2/CTLA-4 correlated with poor OS in AML patients (3-year OS: TGCA data 30% vs 0% and 20% vs 0%, validation group 57% vs 31% and 57% vs 33%, respectively) (P < 0.05). Moreover, co-expression of PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 was found to correlate with poor OS in AML patients with FLT3mut, RUNX1mut, and TET2mut, respectively. In conclusion, high expression of ICs in the BM leukemia cells of AML patients correlated with poor outcome. The co-expression patterns of PD-1/CTLA-4, PD-L2/CTLA-4, PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 might be potential immune biomarkers for designing novel AML therapy.

| S-EPMC7118887 | biostudies-literature

Curcumol Synergizes with Cisplatin in Osteosarcoma by Inhibiting M2-like Polarization of Tumor-Associated Macrophages.

Project description:Osteosarcoma is the most prevalent bone cancer, and chemotherapy is still an indispensable treatment in its clinical practice. Cisplatin (CDDP) has become the most commonly used agent for osteosarcoma, although the outcomes of CDDP chemotherapy remain unsatisfactory because of frequent resistance. Here, we report on a promising combination therapy where curcumol, a bioactive sesquiterpenoid, enhanced CDDP-induced apoptosis to eradicate osteosarcoma cells, and revealed that M2-like macrophages might be the underlying associated mechanisms. First, we observed that curcumol enhanced the CDDP-mediated inhibition of cell proliferation and augmented the apoptosis in osteosarcoma cell lines. Curcumol contributed to preventing the migration of osteosarcoma cells when combined with CDDP. Moreover, this drug combination showed more potent tumor-growth suppression in the orthotopic transplantation of osteosarcoma K7M2 WT cells. We then estimated chemotherapy-associated drug-resistant genes, including ABCB1, ABCC1 and ABCG2, and found that curcumol significantly reversed the mRNA levels of CDDP-induced ABCB1, ABCC1 and ABCG2 genes in the tumor tissue. Moreover, M2-like macrophages were enriched in osteosarcoma tissues, and were largely decreased after curcumol and CDDP treatment. Taken together, these findings suggest that curcumol inhibits the polarization of M2-like macrophages and could be a promising combination strategy to synergize with CDDP in the osteosarcoma.

| S-EPMC9318016 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data