Immune correlates of CD73 expression in patients with urothelial carcinoma (UC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4548-4548
Author(s):  
Edwin Lin ◽  
Roberto Nussenzveig ◽  
Andrew W Hahn ◽  
Mark Yandell ◽  
Lauren Christine Harshman ◽  
...  
Keyword(s):  
Nk Cells ◽  
Immune Evasion ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Statistical Significance ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Cancer Dataset ◽  
Immune Correlates ◽  
Tumor Phenotype

4548 Background: Checkpoint inhibitors have improved outcomes in UC. However, response rates are low and additional mechanisms of immune evasion need to be ascertained. CD73 (encoded by NT5E) converts extracellular AMP to adenosine, which exerts an immunosuppressive effect in the tumor microenvironment by inhibiting infiltrating T and NK cells. Utilizing The Cancer Genome Atlas (TCGA) bladder cancer dataset, we evaluated correlations between NT5E expression and the immune milieu in UC. Methods: RNA-seq data from 411 primary UC tumor samples were obtained from the TCGA. Patients were split into low, intermediate, and high NT5E expression groups (≤ -1, -1 to 1 and ≥1 standard deviation from the overall mean). A tumor inflammation signature (TIS) reflecting an inflamed tumor phenotype was calculated based on the averaged expression of 18 previously validated genes (Ayers et al, 2017). NT5E expression was compared between tumors with high and low TIS scores and among the TCGA molecular subtypes. Abundance of infiltrating immune cell subsets was estimated based on expression of previously identified 782 immune metagenes and compared between NT5E expression groups (Charoentong et al, 2017). The Mann-Whitney U test assessed statistical significance, and the Bonferroni correction was used to control for false discovery rate. Results: NT5E expression was significantly higher in tumors with a high TIS score compared to those with low TIS score (P<0.0001) and correlated with expression of other immune checkpoints such as PD-L1, IDO and LAG-3 (each P<0.01). Patients with basal/squamous subtype had the highest NT5E expression compared to luminal or neuronal subtypes. High NT5E expression was associated with increased infiltrating NK cells, neutrophils, Tregs and decreased Type 2 T helper cells. Conclusions: High expression of NT5E in UC patients with an inflamed tumor phenotype was associated with an increase in infiltrating Tregs, and the basal/squamous subtype. Our findings highlight a potential role of CD73-adenosine pathway as a mechanism of immune evasion and a novel therapeutic target in UC. Further studies to assess the clinical impact of NT5E expression on outcomes in UC patients treated with immunotherapy are needed. AT and NA: equal contribution.

NT5E expression and the immune landscape of prostate cancer (PC): An analysis from The Cancer Genome Atlas database.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16591-e16591
Author(s):  
Abhishek Tripathi ◽  
Edwin Lin ◽  
Roberto Nussenzveig ◽  
Mark Yandell ◽  
Sumanta K. Pal ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
The Cancer Genome Atlas ◽  
Effector Memory ◽  
Marker Genes ◽  
Promote Tumor Growth ◽  
Tumor Phenotype ◽  
Tcga Dataset ◽  
Tumor Expression

e16591 Background: Immune checkpoint inhibitors targeting PD-1/L1 and CTLA-4 pathway have shown modest activity in patients with advanced PC. Additional immunosuppressive mechanisms in the PC tumor microenvironment need to be investigated. Increased CD73 (encoded by NT5E) expression results in generation of immunosuppressive adenosine in the tumor microenvironment and has been associated with metastasis and poor survival in PC. Utilizing the TCGA dataset, we investigated the association of NT5E expression with the immune landscape of PC. Methods: RNA-seq data for 331 PC tumor samples and 51 normal adjacent tissue (NAT) samples was downloaded and log2 transformed. Patients were split into low, intermediate, and high expression groups based on NT5E expression (≤ -1, -1 to 1 and ≥1 standard deviation from the overall mean) in tumor and NAT. A tumor inflammation signature (TIS) reflecting an inflamed tumor phenotype was calculated based on the averaged tumor expression of 18 previously validated genes (Ayers et al, 2017). Abundance of infiltrating immune cell subsets was estimated based on expression of previously identified 782 immune metagenes (Charoentong et al, 2017). Immune cell abundance scores and TIS were compared between NT5E expression groups using the Mann-Whitney U test and the Bonferroni correction was used to control for false discovery rate. Results: NT5E expression in NAT was not associated with the TIS or expression of immune cell marker genes. In contrast, NT5E expression in tumor tissue correlated positively with TIS (P < 0.001). Compared to tumors with low NT5E expression, those in high NT5E expression group had higher expression of central memory CD4+, effector memory CD8+, type 1 helper, NK and regulatory T (Treg) cell markers. Conclusions: In our analysis, NT5E expression correlated with markers of inflamed tumor phenotype in PC. Although NT5E expression was associated with higher CD8+and CD4+ T cells, concurrent increase in Tregs could inhibit the infiltrating lymphocytes and promote tumor growth. Our findings indicate a possible role for the adenosine pathway as a mediator of immunosuppression in PC and a potential therapeutic target. AT and EL: Equal contribution

scholarly journals Landscape of Immune Cell Infiltration in Cervical Cancer

2021 ◽  
Author(s):  
Shasha Shi ◽  
Fu Peng ◽  
Chenghao Yu
Keyword(s):  
Cervical Cancer ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Expression Profiles ◽  
The United States ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Cancer Tissues

Abstract BackgroundCervical cancer is a life-threatening cancer among women. It is the second most prevalent malignant tumor in women. It ranks high in cancer deaths among women worldwide, including in the United States. Immune checkpoint inhibitors have emerged as an important therapeutic approach to treat several cancers, including cervical cancer. Notably, the development and progress of cervical cancer may be related to sustained immune response. This underlines the need to clarify immune cell infiltration (ICI) in cervical cancer tissues. MethodsIn this study, disease-related information of 964 cervical cancer patients was first retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. We utilized bioinformatics data to analyze the expression profiles of immune genes in cervical cancer tissues. ResultsPatients were divided into high and low groups according to ICI score. High ICI scores corresponded with activation of immune signaling pathways and high tumor mutation burden (TMB), which was related to better prognosis of G1-2 cervical cancer. In addition, most immune checkpoints and immuno-related genes such as CD274, CD8A, CXCL10, etc. were over-expressed in the high ICI group. ConclusionsThis study demonstrated that ICI score can accurately predict the prognosis of cervical cancer. Understanding ICI patterns will deepen our understanding of tumor microenvironment (TME) of cervical cancer, which may create the foundation for the development of efficient immunotherapeutic strategies against the cancer.

scholarly journals Hypoxic Characteristic in the Immunosuppressive Microenvironment of Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuomao Mo ◽  
Daiyuan Liu ◽  
Dade Rong ◽  
Shijun Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Immunosuppressive Microenvironment

Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC.Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score.Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts.Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.

GDF15 expression in metastatic colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 116-116
Author(s):  
Priya Jayachandran ◽  
Joanne Xiu ◽  
Shivani Soni ◽  
Richard M. Goldberg ◽  
Benjamin Adam Weinberg ◽  
...  
Keyword(s):  
Colon Cancer ◽  
T Cells ◽  
Nk Cells ◽  
Chromatin Remodeling ◽  
Cancer Progression ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Metastatic Colon Cancer ◽  
Genomic Alterations

116 Background: Cachexia affects many cancer patients. Growth differentiation factor-15 (GDF15) is a protein that regulates weight and the stress response of cells. The GDF15 gene encodes a ligand of TGF-beta that triggers cachexia and modulates the progression from tumorigenesis to metastasis. Inhibition of GDF15 with an antibody restored muscle mass and fat in animal models. Serum levels rise in proportion to the progression of colon cancer, predict outcome, and have been correlated with CEA. Methods: We retrospectively reviewed 7607 CRC tumors profiled by Caris Life Sciences (Phoenix, AZ) from 2019 to 2020. Profiling included whole transcriptome sequencing (RNA-Seq by NovoSeq). Tumor mutational burden, mismatch repair status, and pathway genomic alterations were evaluated. QuantiSEQ was used to assess immune cell infiltration in the tumor microenvironment. Results: GDF15 expression ranged from 0 to 593 transcripts per million (TPM) with median of 30 (IQR = 15.02). There was no association with age, sex, or primary tumor sidedness. MSI-H/dMMR tumors had higher GDF15 expression (median 37 vs 30, p = 0.0004); TMB > = 17 tumors was seen in 5.9% of bottom quartile (Q1) GDF15 expressors and 8.3% of top quartile (Q4). PDL1 IHC positivity was inversely correlated with GDF15 expression (7.1% in Q1 vs. 2.6% in Q4, p < 0.0001). Genomic alterations associated with higher GDF15 expression (Q4 vs Q1) included genes on TGF-B (SMAD2/4), PI3K (PIK3CA, MTOR), chromatin remodeling (ARID1A, KMT2C), DDR (ATM) and Wnt pathway (APC); those inversely associated included MYC CNA and TP53. Q1 tumors had higher CNA of ERBB2 and FGFR1. Relative neutrophils and NK cells in the TME increased from Q1 to Q4 (p < 0.001). There was a decrease in CD8+ T-cells and Treg cells from Q1 to Q4. Conclusions: GDF15 expression correlates with increased dMMR/MSI-H and TMB, but not with PDL1 expression. Mutations and activated pathways associated with GDF15 expression may explain increased cachexia with more aggressive disease. The association with chromatin remodeling may warrant therapies targeting histone modification and epigenetics. The increase in NK cells but decrease in CD8+ T cells in the TME with increasing GDF15 suggests approaches to treatment. Higher CD8+ lymphocyte counts correlate with PFS with immunotherapy. Anti-PD-L1 therapy reinvigorates the killing function of CD8+ T cells. The decrease in CD8+ T cells and PDL1 positivity with rising GDF15 suggests worse outcome and a lack of response to anti-PDL1 therapy. NK cell checkpoint inhibitors, CARs, and an anti-GFRAL antibody are now in clinical trials and might be utilized in high GDF15 cancers. GDF15 is emerging as a target in the treatment of obesity and cachexia and as a prognostic marker in oncology. Understanding its expression in metastatic colon cancer may reveal which patients could benefit from developing anti-GDF15 targeted therapies against cancer progression.

scholarly journals Immunogenomic Analyses of the Prognostic Predictive Model for Patients With Renal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Feng ◽  
Jiahui Zhao ◽  
Dechao Wei ◽  
Pengju Guo ◽  
Xiaobing Yang ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Predictive Model ◽  
Risk Score ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Immune Checkpoints ◽  
Survival Outcomes ◽  
Prognostic Signature ◽  
Therapeutic Benefits

BackgroundRenal cell carcinoma (RCC) is associated with poor prognostic outcomes. The current stratifying system does not predict prognostic outcomes and therapeutic benefits precisely for RCC patients. Here, we aim to construct an immune prognostic predictive model to assist clinician to predict RCC prognosis.MethodsHerein, an immune prognostic signature was developed, and its predictive ability was confirmed in the kidney renal clear cell carcinoma (KIRC) cohorts based on The Cancer Genome Atlas (TCGA) dataset. Several immunogenomic analyses were conducted to investigate the correlations between immune risk scores and immune cell infiltrations, immune checkpoints, cancer genotypes, tumor mutational burden, and responses to chemotherapy and immunotherapy.ResultsThe immune prognostic signature contained 14 immune-associated genes and was found to be an independent prognostic factor for KIRC. Furthermore, the immune risk score was established as a novel marker for predicting the overall survival outcomes for RCC. The risk score was correlated with some significant immunophenotypic factors, including T cell infiltration, antitumor immunity, antitumor response, oncogenic pathways, and immunotherapeutic and chemotherapeutic response.ConclusionsThe immune prognostic, predictive model can be effectively and efficiently used in the prediction of survival outcomes and immunotherapeutic responses of RCC patients.

scholarly journals A natural killer cell gene signature predicts melanoma patient survival

2018 ◽  
Author(s):  
Joseph Cursons ◽  
Fernando Souza-Fonseca-Guimaraes ◽  
Ashley Anderson ◽  
Momeneh Foroutan ◽  
Soroor Hediyeh-Zadeh ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Solid Tumors ◽  
Immune Cell ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Activity ◽  
Human Tumors ◽  
The Cancer Genome Atlas ◽  
Cell Gene

AbstractAnimal models have demonstrated that natural killer (NK) cells can limit the metastatic dissemination of tumors, however their ability to combat established human tumors has been difficult to investigate.A number of computational methods have been developed for the deconvolution of immune cell types within solid tumors. We have taken the NK cell gene signatures from several tools, then curated and expanded this list using recent reports from the literature. Using a gene set scoring method to investigate RNA-seq data from The Cancer Genome Atlas (TCGA) we show that patients with metastatic cutaneous melanoma have an improved survival rate if their tumor shows evidence of greater NK cell infiltration. Furthermore, these survival effects are enhanced in tumors which have a higher expression of NK cell stimuli such as IL-15, suggesting NK cells are part of a coordinated immune response within these patients. Using this signature we then examine transcriptomic data to identify tumor and stromal components which may influence the penetrance of NK cells into solid tumors.These data support a role for NK cells in the regulation of human tumors and highlight potential survival effects associated with increased NK cell activity. Furthermore, our computational analysis identifies a number of potential targets which may help to unleash the anti-tumor potential of NK cells as we enter the age of immunotherapy.

scholarly journals Combinatorial immunotherapies overcome MYC-driven immune evasion

2021 ◽  
Author(s):  
Joyce V. Lee ◽  
Filomena Houseley ◽  
Christina Yau ◽  
Daniel Van de Mark ◽  
Rachel Nakagawa ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Immune Evasion ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Cell ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Mhc I ◽  
Number Of Patients ◽  
Tumor Outgrowth

For many human cancers, including triple negative breast cancer (TNBC), a modest number of patients benefit from immune checkpoint inhibitors, and few experience cancer remission. Expression of programed death-ligand 1 (PD-L1), tumor immune infiltration, or tumor mutation burden have been widely investigated for predicting cancer immunotherapy response. Whether specific oncogenes diminish response to immunotherapy and whether these effects are reversible remains poorly understood. We predicted that MYC, an oncogene that is frequently overexpressed and is associated with worse prognosis, may predict immunotherapy response in patients with TNBC. Here, we report that MYC-elevated TNBCs are resistant to immune checkpoint inhibitors. Using mouse models of TNBC and patient data we report that MYC signaling is associated with low tumor cell PD-L1, low overall immune cell infiltration, and low tumor cell MHC-I expression. Restoring interferon signaling in the tumor reduces MYC expression and increases MHC-I expression. By combining a TLR9 agonist and an agonistic antibody against OX40 with anti-PD-L1, most mice experience complete tumor regression and are protected from new TNBC tumor outgrowth. Our findings demonstrate that MYC-dependent immune evasion is reversible and druggable, and if strategically targeted, may improve outcomes for patients treated with immune checkpoint inhibitors.

scholarly journals Epigenetic Modifiers: Anti-Neoplastic Drugs With Immunomodulating Potential

2021 ◽  
Vol 12 ◽  
Author(s):  
Ken Maes ◽  
Anna Mondino ◽  
Juan José Lasarte ◽  
Xabier Agirre ◽  
Karin Vanderkerken ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Evasion ◽  
Cell Biology ◽  
Tumor Antigens ◽  
Immune Cell ◽  
Peripheral Tolerance ◽  
Immune Checkpoints ◽  
Host Immune System ◽  
Innate Defense ◽  
Cell Functions

Cancer cells are under the surveillance of the host immune system. Nevertheless, a number of immunosuppressive mechanisms allow tumors to escape protective responses and impose immune tolerance. Epigenetic alterations are central to cancer cell biology and cancer immune evasion. Accordingly, epigenetic modulating agents (EMAs) are being exploited as anti-neoplastic and immunomodulatory agents to restore immunological fitness. By simultaneously acting on cancer cells, e.g. by changing expression of tumor antigens, immune checkpoints, chemokines or innate defense pathways, and on immune cells, e.g. by remodeling the tumor stroma or enhancing effector cell functionality, EMAs can indeed overcome peripheral tolerance to transformed cells. Therefore, combinations of EMAs with chemo- or immunotherapy have become interesting strategies to fight cancer. Here we review several examples of epigenetic changes critical for immune cell functions and tumor-immune evasion and of the use of EMAs in promoting anti-tumor immunity. Finally, we provide our perspective on how EMAs could represent a game changer for combinatorial therapies and the clinical management of cancer.

scholarly journals Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Sihui Yu ◽  
Xi Li ◽  
Jiawen Zhang ◽  
Sufang Wu
Keyword(s):  
Cervical Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Patient Survival ◽  
Checkpoint Inhibitors ◽  
Cell Types ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cervical Lesions ◽  
Immune Infiltration

Predictive models could indicate the clinical outcome of patients with carcinoma. Cervical cancer is one of the most frequently diagnosed female malignancies. Herein, we proposed an immune infiltration-related gene signature that predicts prognosis of patients with cervical cancer and depicts the immune landscape as well. We utilized the transcriptome data of The Cancer Genome Atlas (TCGA) and estimated the infiltration level of 28 immune cell types. We screened out four immune cell types conducive to patient survival and recognized their shared differentially expressed genes (DEGs). Four core genes (CHIT1, GTSF1L, PLA2G2D, and GNG8) that composed the ultimate signature were identified via univariate and multivariate Cox regression. The optimal model we built up could distinguish patients with cervical cancer into high-score and low-score subgroups. These two subgroups showed disparity in aspects of patient survival, immune infiltration landscape, and response to immune checkpoint inhibitors. Additionally, we found that GTSF1L was decreased gradually along with the severity of cervical lesions, and its potential role in immune contexture and clinical practice were also demonstrated. Our results suggested that the Immunoscore based on four immune-related genes could serve as a supplementary criterion to effectively foresee the survival outcome, tumor infiltration status, and immunotherapy efficacy of cervical cancer patients.

scholarly journals Three Immune-Associated Subtypes of Diffuse Glioma Differ in Immune Infiltration, Immune Checkpoint Molecules, and Prognosis

2020 ◽  
Vol 10 ◽  
Author(s):  
Quanwei Zhou ◽  
Xuejun Yan ◽  
Weidong Liu ◽  
Wen Yin ◽  
Hongjuan Xu ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cox Regression ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Immune Checkpoints ◽  
Signal Pathways ◽  
Diffuse Glioma ◽  
Immune Infiltration ◽  
Immune Related Genes

Diffuse glioma is one of the most prevalent malignancies of the brain, with high heterogeneity of tumor-infiltrating immune cells. However, immune-associated subtypes of diffuse glioma have not been determined, nor has the effect of different immune-associated subtypes on disease prognosis and immune infiltration of diffuse glioma patients. We retrieved the expression profiles of immune-related genes from The Cancer Genome Atlas (TCGA) (n = 672) and GSE16011 (n = 268) cohorts and used them to identify subtypes of diffuse glioma via Consensus Cluster Plus analysis. We used the limma, clusterProfiler, ESTIMATE, and survival packages of R for differential analysis, functional enrichment, immune and stromal score evaluation respectively in three subtypes, and performed log-rank tests in immune subtypes of diffuse glioma. The immune-associated features of diffuse glioma in the two cohorts were characterized via bioinformatic analyses of the mRNA expression data of immune-related genes. Three subtypes (C1–3) of diffuse glioma were identified from TCGA data, and were verified using the GSE16011 cohort. We then evaluated their immune characteristics and clinical features. Our mRNA profiling analyses indicated that the different subtypes of diffuse glioma presented differential expression profile of specific genes and signal pathways in the TCGA cohort. Patients with subtype C1, who were mostly diagnosed with grade IV glioma, had poorer outcomes than patients with subtype C2 or C3. Subtype C1 was characterized by a higher degree of immune cell infiltration as estimated by GSVA, and more frequent wildtype IDH1. By contrast, subtype C3 included more grade II and IDH1-mutated glioma, and was associated with more infiltration of CD4+T cells. Most subtype C2 had the features between subtypes C1 and C3. Meanwhile, immune checkpoints and their ligand molecules, including PD1/(PD-L1/PDL2), CTLA4/(CD80/CD86), and B7H3/TLT2, were significantly upregulated in subtype C1 and downregulated in subtype C3. In addition, patients with subtype C1 exhibited more frequent gene mutations. Univariate and multivariate Cox regression analyses revealed that diffuse glioma subtype was an effective, independent, and better prognostic factor. Therefore, we established a novel immune-related classification of diffuse glioma, which provides potential immunotherapy targets for diffuse glioma.

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