Development and validation of an immunogenic cell death-related prognostic model, and landscape of the tumor immune microenvironment in glioblastoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Yang S
PROVIDER: S-EPMC10806272 | biostudies-literature | 2024 May
REPOSITORIES: biostudies-literature
Publications
Development and validation of an immunogenic cell death-related prognostic model, and landscape of the tumor immune microenvironment in glioblastoma.
Yang Sha S Deng Mei M Xiong Yunbiao Y Xiong Bing B Fu Junwu J Wang Jia J Zhang Jiqin J Han Guoqiang G Liu Jian J Tan Ying Y
Genes & diseases 20230628 3
Similar Datasets
Project description:Emerging evidence indicates that the induction of radiotherapy(RT) on the immunogenic cell death (ICD) is not only dependent on its direct cytotoxic effect, changes in the tumor immune microenvironment also play an important role in it. Tumor immune microenvironment (TIME) refers to the immune microenvironment that tumor cells exist, including tumor cells, inflammatory cells, immune cells, various signaling molecules and extracellular matrix. TIME has a barrier effect on the anti-tumor function of immune cells, which can inhibit all stages of anti-tumor immune response. The remodeling of TIME caused by RT may affect the degree of immunogenicity, and make it change from immunosuppressive phenotype to immunostimulatory phenotype. It is of great significance to reveal the causes of immune escape of tumor cells, especially for the treatment of drug-resistant tumor. In this review, we focus on the effect of RT on the TIME, the mechanism of RT in reversing the TIME to suppress intrinsic immunity, and the sensitization effect of the remodeling of TIME caused by RT on the effectiveness of immunotherapy.
| S-EPMC9753984 | biostudies-literature
Project description:Pancreatic cancer (PC) is a malignancy of the gastrointestinal tract that is characterized by a poor prognosis. This study investigates the roles of immunogenic cell death (ICD) genes in the prognosis and progression of PC. Expression data for PC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, while ICD genes were sourced from published literature. We explored the expression patterns and identified two distinct clusters based on ICD genes. Kaplan-Meier analysis, differential expression analysis, tumor mutational burden analysis, and immune cell infiltration analysis were performed on these clusters. An ICD gene-based risk model was developed, categorizing samples from the TCGA and GEO datasets into low- and high-risk groups. Additionally, we investigated the expression levels of the genes included in the risk model within the TCGA cohort and our own samples. Finally, a loss-of-function assay was conducted to assess the role of MYD88 in PC. Two clusters of PC samples were identified, patients in the ICD-low cluster exhibited a higher degree of immune cell enrichment. The survival time of patients in the low-risk group was longer than that of those in the high-risk group. The genes included in the risk model (CASP1, MYD88, and PIK3CA) showed upregulated expression levels in tumor samples. Furthermore, the predictive accuracy of our risk model was validated using our own samples. Genetic inhibition of MYD88 led to significantly decreased proliferation and migration of PC cells in the loss-of-function assay. There were disparities in survival time and tumor immune microenvironment (TIME) between two ICD gene clusters. Additionally, we developed an ICD-related risk model that was validated as an independent prognostic indicator for patients with PC.
| S-EPMC11663176 | biostudies-literature
Project description:The tumor microenvironment is closely related to the progression and immune escape of tumor cells. Tumor-infiltrating immune cells (TIICs) and immune-related genes (IRGs) are indispensable components of the tumor microenvironment and have been demonstrated to be highly valuable in determining the prognosis of multiple cancers. To elucidate the prognostic value of TIICs and IRGs in gastric cancer, we conducted a comprehensive analysis focusing on the abundances of 22 types of TIICs and differentially expressed IRGs based on a dataset from The Cancer Genome Atlas (TCGA). The results showed that great composition differences in TIICs and immune cell subfractions were associated with survival outcomes in different stages. Additionally, 29 hub genes were characterized from 345 differentially expressed IRGs and found to be significantly associated with survival outcomes. Then, an independent prognostic indicator based on ten IRGs was successfully constructed after multivariate adjustment for some clinical parameters. Further validation revealed that these hub IRGs could reflect the infiltration levels of immune cells. Thus, our results confirmed the clinical significance of TIICs and IRGs in gastric cancer and may establish a foundation for further exploring immune cell and gene targets for personalized treatment.
| S-EPMC7585095 | biostudies-literature
Project description:Cutaneous melanoma (CM) is one of the most life-threatening tumors. Although targeted therapies and immune checkpoint inhibitors have significantly improved patient outcomes over the past decades, they still have their efficacy limitations. Immunogenic cell death (ICD) induces regulated cell death through immunogenic signal secretion and exposure. Accumulated evidence suggests that the ICD process is an effective target for the treatment of a variety of tumor types, including CM. However, the research on ICD in CM is far from complete, and its clinical value has not been widely concerned. By analyzing the Cancer Genome Atlas (TCGA) database, we constructed a new risk model based on 4 ICD-related genes and validated its ability to predict the prognosis of CM patients. In addition, we comprehensively analyzed the tumor microenvironment (TME) of CM patients and showed a significant immunosuppressive TME in the high-risk group compared with the low-risk group. By Immunophenoscore (IPS), we further explored the correlation between the model and immunotherapy response. The data of Genomics of Drug Sensitivity in Cancer (GDSC) database were further extracted to analyze drug sensitivity and evaluate its correlation with the established risk model. In the end, differential expressed genes (DEGs) were analyzed by Gene Set Variation Analysis (GSVA) to preliminarily explore the possible signaling pathways related to the prognosis of ICD and CM. The results of this study provide new perspectives and insights for individualized and accurate treatment strategies for CM patients.
| S-EPMC9532744 | biostudies-literature
Project description:IntroductionUveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, and the main treatment for UM is currently surgery and plaque brachytherapy. UM is highly susceptible to metastasis, which eventually occurs in nearly half of all patients; once metastasis occurs, patients have a poor prognosis and the condition is difficult to treat. Therefore, the identification of new and effective UM biomarkers is vital for the application of therapeutic strategies. Immunogenic cell death (ICD) is a type of regulatory cell death that activates adaptive immune responses and generates long-term immunological memory. ICD can promote antitumor immunity, which may be a potential immunotherapeutic strategy for UM.MethodsThe data of UM from the Cancer Genome Atlas (TCGA) was used as a training set and the data from Gene Expression Omnibus (GEO) was used as a validation set. To determine the expression pattern of ICD-related genes in UM, survival analysis and difference analysis was conducted. The ICD-related risk signature was constructed by employing the least absolute shrinkage and selection operator (LASSO) Cox regression. Subsequently, immune profile and somatic mutation analysis were performed. In addition, cell experiments were performed to verify the role of immunogenic cell death-related genes in UM.ResultsIn this study, we analyzed the relationship between ICD-related gene expression and UM patient prognosis, somatic mutations, and the tumor immune microenvironment. Importantly, we constructed a 5-gene ICD-related risk signature and confirmed it as a novel prognostic biomarker in UM patients. We found that the high-risk group had more immune cell infiltration and a worse prognosis than the low-risk group. In cellular experiments, we confirmed the high expression of FOXP3 inMUM2B andOCM-1A cell lines and that knockdown of FOXP3 markedly inhibited the proliferation of UM tumor cells.DiscussionICD-related genes play a critical role in the tumor immune microenvironment. Our results may contribute to the development of effective immunotherapies.
| S-EPMC9709208 | biostudies-literature
Project description:Tumor immunotherapy is only effective in a fraction of patients due to a low response rate and severe side effects, and these challenges of immunotherapy in clinics can be addressed through induction of immunogenic cell death (ICD). ICD is elicited from many antitumor therapies to release danger associated molecular patterns (DAMPs) and tumor-associated antigens to facilitate maturation of dendritic cells (DCs) and infiltration of cytotoxic T lymphocytes (CTLs). The process can reverse the tumor immunosuppressive microenvironment to improve the sensitivity of immunotherapy. Nanostructure-based drug delivery systems (NDDSs) are explored to induce ICD by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) for photodynamic therapy (PDT), photothermal conversion agents for photothermal therapy (PTT), and radiosensitizers for radiotherapy (RT). These NDDSs can release loaded agents at a right dose in the right place at the right time, resulting in greater effectiveness and lower toxicity. Immunotherapeutic agents can also be combined with these NDDSs to achieve the synergic antitumor effect in a multi-modality therapeutic approach. In this review, NDDSs are harnessed to load multiple agents to induce ICD by chemotherapy, PDT, PTT, and RT in combination of immunotherapy to promote the therapeutic effect and reduce side effects associated with cancer treatment.
| S-EPMC9353475 | biostudies-literature
Project description:Preclinical and clinical studies have validated the antitumor effects of several oncolytic viruses (OVs). However, the efficacy of OVs is limited when they are administered as monotherapies. Combination therapy is a promising direction for oncolytic virotherapy in the future. A high dose of vitamin C (VitC) exerts anticancer effects by triggering the accretion of substantial amounts of reactive oxygen species (ROS). OVs can induce immunogenic tumor cell death and elicit an antitumor immune response. ROS play an important role in immunogenic cell death (ICD). This study aimed to explore whether high-dose VitC in combination with oncolytic adenoviruses (oAds) exhibited a synergistic antitumor effect. High-dose VitC synergized with oAds against tumor by enhancing immunogenic tumor cell death. Combination therapy with high-dose VitC and oAds significantly increased the number of T cells in the tumor microenvironment (TME) and promoted the activation of T cells. Furthermore, the antitumor effect of the combination therapy was CD8+ T cell dependent. In addition, combination therapy with high-dose VitC and oAds reprogramed the immunosuppressive TME. Our study provides a new strategy for combination therapy of OVs.
| S-EPMC8821933 | biostudies-literature
Project description:Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic malignancies, and effective treatments are still lacking due to drug tolerance and tumor recurrence. In this study, we aimed to investigate the effects of sonodynamic therapy (SDT) on ovarian cancer and its potential mechanism. Folate receptor-targeted and ultrasound-responsive nanoparticles (NPs) were constructed using PLGA-PEG-FA (PLGA: poly (lactic-co-glycolic) acid, polyethylene glycol (PEG), FA: folate), the reactive oxygen species (ROS)-generating sonosensitizer IR780 and the oxygen-carrying material perfluorohexane (PFH), termed IRO@FA NPs. The antitumor effect of NPs triggered by ultrasound (US) was measured by an apoptosis assay in a C57/BL6 mouse model. Immunochemistry and flow cytometry were used to detect the proportion of CD3+ T, CD4+ T, CD8+ T cells and activated dendritic cells (DCs) in spleens and tumor tissues to assess variation in the immune response. Moreover, endoplasmic reticulum (ER) stress and immunogenic cell death (ICD) markers (high mobility group protein box-1, ATP and calreticulin) were detected to identify potential mechanisms. The results showed that IRO@FA NP-mediated SDT promoted ID8 cell apoptosis both in vitro and in vivo. The densities of CD3+ and CD8+ T lymphocytes and inflammatory markers were upregulated in tumor tissues. IRO@FA NP-mediated SDT prompted DC maturation and T lymphocyte infiltration by inducing ID8 cell ICD.
| S-EPMC9004507 | biostudies-literature
Project description:The tumor microenvironment (TME) has been shown to be involved in angiogenesis, tumor metastasis, and immune response, thereby affecting the treatment and prognosis of patients. This study aims to identify genes that are dysregulated in the TME of patients with colon adenocarcinoma (COAD) and to evaluate their prognostic value based on RNA omics data. We obtained 512 COAD samples from the Cancer Genome Atlas (TCGA) database and 579 COAD patients from the independent dataset (GSE39582) in the Gene Expression Omnibus (GEO) database. The immune/stromal/ESTIMATE score of each patient based on their gene expression was calculated using the ESTIMATE algorithm. Kaplan-Meier survival analysis, Cox regression analysis, gene functional enrichment analysis, and protein-protein interaction (PPI) network analysis were performed. We found that immune and stromal scores were significantly correlated with COAD patients' overall survival (log rank p < 0.05). By comparing the high immune/stromal score group with the low score group, we identified 688 intersection differentially expressed genes (DEGs) from the TCGA dataset (663 upregulated and 25 downregulated). The functional enrichment analysis of intersection DEGs showed that they were mainly enriched in the immune process, cell migration, cell motility, Toll-like receptor signaling pathway, and PI3K-Akt signaling pathway. The hub genes were revealed by PPI network analysis. Through Kaplan-Meier and Cox analysis, four TME-related genes that were significantly related to the prognosis of COAD patients were verified in GSE39582. In addition, we uncovered the relationship between the four prognostic genes and immune cells in COAD. In conclusion, based on the RNA expression profiles of 1091 COAD patients, we screened four genes that can predict prognosis from the TME, which may serve as candidate prognostic biomarkers for COAD.
| S-EPMC8762242 | biostudies-literature
Project description:Stomach adenocarcinoma (STAD) ranks as the fourth prevalent cause of mortality worldwide due to cancer. The prognosis for those suffering from STAD was bleak. Immunogenic cell death (ICD), a form of induced cellular death that causes an adaptive immune response and has increasing in anticancer treatment. However, it has not been ascertained how ICD-related lncRNAs affect STAD. Using univariate Cox regression and the TCGA database, lncRNAs with prognostic value were identified. Thereafter, we created a prognostic lncRNA-based model using LASSO. Kaplan-Meier assessment, time-dependent receiver operating characteristic (ROC) analyzation, independent prognostic investigation, and nomogram were used to assess model correctness. Additional research included evaluations of the immunological microenvironment, gene set enrichment analyses (GSEA), tumor mutation burdens (TMBs), tumor immune dysfunctions and exclusions (TIDEs), and antitumor compounds IC50 predictions. We found 24 ICD-related lncRNAs with prognostic value via univariate Cox analysis (p < 0.05). Subsequently, a risk model was proposed using five lncRNAs relevant to ICD. The risk signature, correlated with immune cell infiltration, had strong predictive performance. Individuals at low-risk group outlived those at high risk (p < 0.001). An evaluation of the 5-lncRNA risk mode including ROC curves, nomograms, and correction curves confirmed its predictive capability. The findings of functional tests revealed a substantial alteration in immunological conditions and the IC50 sensitivity for the two groups. Using five ICD-related lncRNAs, the authors developed a new risk model for STAD patients that could predict their cumulative overall survival rate and guide their individual treatment.
| S-EPMC9614277 | biostudies-literature