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      Integrated analysis reveals the potential of cluster of differentiation 86 as a key biomarker in high-grade glioma

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          Abstract

          This study aimed to evaluate the potential of cluster of differentiation 86 (CD86) as a biomarker in high-grade glioma (HGG). The TCGA and TCIA databases were used to obtain the CD86 expression value, clinical data, and MRI images of HGG patients. Prognostic values were assessed by the Kaplan-Meier method, Receiver operating characteristic curve (ROC), Cox regression, logistic regression, and nomogram analyses. CD86-associated pathways were also explored. We found that CD86 was significantly upregulated in HGG compared with the normal group. Survival analysis showed a significant association between CD86 high expression and shorter overall survival time. Its independent prognostic value was also confirmed. These results suggested the possibility of CD86 as a biomarker in HGG. We also innovatively established 2 radiomics models with Support Vector Machine (SVM) and Logistic regression (LR) algorithms to predict the CD86 expression. The 2 models containing 5 optimal features by SVM and LR methods showed similar favorable performance in predicting CD86 expression in the training set, and their performance were also confirmed in validation set. These results indicated the successful construction of a radiomics model for non-invasively predicting biomarker in HGG. Finally, pathway analysis indicated that CD86 might be involved in the natural killer cell-mediated cytotoxicity in HGG progression.

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          Immunotherapy for glioma: current management and future application

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            Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons

            The main breakthrough in tumor immunotherapy was the discovery of immune checkpoint (IC) proteins, which act as a potent suppressor of the immune system by a myriad of mechanisms. After that, scientists focused on the immune checkpoint molecules mainly. Thereby, much effort was spent to progress novel strategies for suppressing these inhibitory axes, resulting in the evolution of immune checkpoint inhibitors (ICIs). Then, ICIs have become a promising approach and shaped a paradigm shift in tumor immunotherapies. CTLA-4 plays an influential role in attenuation of the induction of naïve and memory T cells by engagement with its responding ligands like B7-1 (CD80) and B7-2 (CD86). Besides, PD-1 is predominantly implicated in adjusting T cell function in peripheral tissues through its interaction with programmed death-ligand 1 (PD-L1) and PD-L2. Given their suppressive effects on anti-tumor immunity, it has firmly been documented that ICIs based therapies can be practical and rational therapeutic approaches to treat cancer patients. Nonetheless, tumor inherent or acquired resistance to ICI and some treatment-related toxicities restrict their application in the clinic. The current review will deliver a comprehensive overview of the ICI application to treat human tumors alone or in combination with other modalities to support more desired outcomes and lower toxicities in cancer patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12964-022-00854-y.
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              Ferroptosis, as the most enriched programmed cell death process in glioma, induces immunosuppression and immunotherapy resistance

              Immunosuppressive microenvironment is a major cause of immunotherapeutic resistance in glioma. In addition to secreting compounds, tumor cells under programmed cell death (PCD) processes release abundant mediators to modify the neighboring microenvironment. However, the complex relationship among PCD status, immunosuppressive microenvironment, and immunotherapy is still poorly understood. Four independent glioma cohorts comprising 1,750 patients were enrolled for analysis. The relationships among PCD status, microenvironment cellular components, and biological phenotypes were fully explored. Tissues from our hospital and experiments in vitro and in vivo were used to confirm the role of ferroptosis in glioma. Analyses to determine enriched PCD processes showed that ferroptosis was the main type of PCD in glioma. Enriched ferroptosis correlated with progressive malignancy, poor outcomes, and aggravated immunosuppression in glioblastoma (GBM) patients. Enhanced ferroptosis was shown to induce activation and infiltration of immune cells but attenuated antitumor cytotoxic killing. Tumor-associated macrophages (TAMs) were found to participate in ferroptosis-mediated immunosuppression. Preclinically, ferroptosis inhibition combined with Programmed Cell Death 1 (PD-1) and Programmed Cell Death Ligand-1 (PD-L1) blockade generated a synergistic therapeutic outcome in GBM murine models. This work provides a molecular, clinical, and biological landscape of ferroptosis, suggesting a role of ferroptosis in glioma malignancy and a novel synergic immunotherapeutic strategy that combines immune checkpoint blockade treatment with ferroptosis inhibition.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                31 December 2023
                26 December 2023
                : 15
                : 24
                : 15402-15418
                Affiliations
                [1 ]Department of Anesthesiology, Ningbo Medical Center Lihuili Hospital, Ningbo 315100, Zhejiang, China
                [2 ]Department of Radiology, Ningbo Medical Center Lihuili Hospital, Ningbo 315100, Zhejiang, China
                [3 ]Department of Neurosurgery, Ningbo Medical Center Lihuili Hospital, Ningbo 315100, Zhejiang, China
                Author notes
                [*]

                Equal contribution and co-first authorship

                Correspondence to: Gengfan Ye; email: lhlyegengfan@nbu.edu.cn
                Correspondence to: Maosong Chen; email: chenmaosong0416@126.com, https://orcid.org/0000-0001-6863-2352
                Article
                205359 205359
                10.18632/aging.205359
                10781505
                38154107
                8bcfb88a-f7e4-449b-a13a-c9503827e36c
                Copyright: © 2023 Wen et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 08 September 2023
                : 16 November 2023
                Categories
                Research Paper

                Cell biology
                cd86,high-grade glioma,biomarker,prognosis,radiomics
                Cell biology
                cd86, high-grade glioma, biomarker, prognosis, radiomics

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