Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer

Zhang, Hao; Dai, Ziyu; Wu, Wantao; Wang, Zeyu; Zhang, Nan; Zhang, Jintao; Zeng, Wenjing; Liu, Zhixiong; Cheng, Quan

doi:10.1186/s13046-021-01987-7

Cited by 295 publications

(219 citation statements)

References 258 publications

(272 reference statements)

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“…Glioma is a central nervous system-derived tumor with highly aggressive growth pattern, treatment resistance, and poor prognosis. Nowadays, strategies show their limitations on improving patient's survival outcome, including surgery, chemotherapy, and radiotherapy (23). To reveal the mechanism concealed behind its aggressive growth pattern, we identify HOXA5 as prognostic-related genes through regulating cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

HOXA5 Is Recognized as a Prognostic-Related Biomarker and Promotes Glioma Progression Through Affecting Cell Cycle

Ding¹,

Chen²,

Bie³

et al. 2021

Front. Oncol.

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Glioma is malignant tumor derives from glial cells in the central nervous system. High-grade glioma shows aggressive growth pattern, and conventional treatments, such as surgical removal and chemo-radiotherapy, archive limitation in the interference of this process. In this work, HOXA5, from the HOX family, was identified as a glioma cell proliferation-associated factor by investigating its feature in the TCGA and CGGA data set. High HOXA5 expression samples contain unfavorable clinical features of glioma, including IDH wild type, un-methylated MGMT status, non-codeletion 1p19q status, malignant molecular subtype. Survival analysis indicates that high HOXA5 expression samples are associated with worse clinical outcome. The CNVs and SNPs profile difference further confirmed the enrichment of glioma aggressive related biomarkers. In the meantime, the activation of DNA damage repair-related pathways and TP53-related pathways is also related to HOXA5 expression. In cell lines, U87MG and U251, by interfering HOXA5 expression significantly inhibit glioma progression and apoptosis, and cell cycle is arrested at the G2/M phase. Collectively, increased HOXA5 expression can promote glioma progression via affecting glioma cell proliferation.

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Section: Discussionmentioning

confidence: 99%

HOXA5 Is Recognized as a Prognostic-Related Biomarker and Promotes Glioma Progression Through Affecting Cell Cycle

Ding¹,

Chen²,

Bie³

et al. 2021

Front. Oncol.

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“…CTLA-4 is a kind of representative immune checkpoint pathway like PD-1/PD-L1 and is also involved in the negative regulation of immune function at different stages of T cell activation [ 13 ]. CTLA-4, expressed on activated T and Treg cells, is homologous to CD28 and has a higher affinity for CD80 and CD86 [ 40 ].…”

Section: Ctla-4mentioning

confidence: 99%

“…Thus, targeted immune checkpoint therapy is a new hot spot in tumor immunotherapy. Immune checkpoint inhibitors (ICIs) mediated immunotherapy has become a turning point in oncology therapy by targeting immune checkpoints, relieving T cell suppression, and promoting antitumor immunity [ 13 , 14 ]. So far, the cytotoxic T-lymphocyte antigen, 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) are the main representative immune checkpoints.…”

Section: Introductionmentioning

confidence: 99%

“…So far, the cytotoxic T-lymphocyte antigen, 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) are the main representative immune checkpoints. Meanwhile, Lymphocyte activation-gene-3 (LAG-3), T cell immunoglobulin domain and mucin domain-3 (TIM-3), and T cell immunoreceptor with Ig and Itim domains (TIGIT) have been identified ( Table 1 ) [ 13 , 15 , 16 ]. In the case of pituitary tumors, with the further study of its immune microenvironment, the use of immune checkpoint inhibitors may be the next effective choice for the treatment of refractory pituitary tumors or even pituitary cancer.…”

Section: Introductionmentioning

confidence: 99%

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Immune Checkpoints: Therapeutic Targets for Pituitary Tumors

et al. 2021

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Pituitary tumors are the third most common intracranial tumors in adults. Treatment of refractory pituitary tumors is known to be difficult due to limited treatment options. As a promising therapeutic method, tumor immunotherapy has been applied in the treatment of many tumors, including pituitary tumors. Immune checkpoint blocking is one of the effective strategies to activate antitumor immunity. Immune checkpoints prevent tissue damage by regulating the immune response of peripheral tissues and participate in the maintenance of a normal immune environment. In the presence of a tumor, inhibition of T cell activity by tumor cells binding to immune checkpoints and their ligands is an important mechanism for tumor cells to escape immune injury. In this review, we summarize the latest findings of immune checkpoints and their potential as immunotherapeutic targets for pituitary tumors.

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“…Immune checkpoint blockers such as PD-1/L1 and CTLA-4 have demonstrated remarkable clinical efficacy in the management of multiple cancers ( 2 , 3 ). However, the current checkpoint immunotherapy is only effective in a limited number of glioma patients.…”

Section: Introductionmentioning

confidence: 99%

Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment

Zhang

Wang

et al. 2021

Front. Immunol.

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The glioma tumor microenvironment (TME), composed of several noncancerous cells and biomolecules is known for its complexity of cancer-immune system interaction. Given that, novel risk signature is required for predicting glioma patient responses to immunotherapy. In this study, we systematically evaluated the TME infiltration pattern of 2877 glioma samples. TME phenotypes were determined using the Partitioning Around Medoid method. Machine learning including SVM-RFE and Principal component analysis (PCA) were used to construct a TME scoring system. A total of 857 glioma samples from four datasets were used for external validation of the TME-score. The correlation of TME phenotypes and TME-scores with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in glioma patients was determined. Immunohistochemistry staining for the M2 macrophage marker CD68 and CD163, mast cell marker CD117, neutrophil marker CD66b, and RNA sequencing of glioma samples from the XYNS cohort were performed. Two distinct TME phenotypes were identified. High TME-score correlated with a high number of immune infiltrating cells, elevated expression of immune checkpoints, increased mutation rates of oncogenes, and poor survival of glioma patients. Moreover, high TME-score exhibited remarkable association with multiple immunomodulators that could potentially mediate immune escape of cancer. Thus, the TME-score showed the potential to predict the efficacy of anti-PD-1 immunotherapy. Univariate and multivariate analyses demonstrated the TME-score to be a valuable prognostic biomarker for gliomas. Our study demonstrated that TME could potentially influence immunotherapy efficacy in melanoma patients whereas its role in immunotherapy of glioma patients remains unknown. Therefore, a better understanding of the TME landscape in gliomas would promote the development of novel immunotherapy strategies against glioma.

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Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer

Cited by 295 publications

References 258 publications

HOXA5 Is Recognized as a Prognostic-Related Biomarker and Promotes Glioma Progression Through Affecting Cell Cycle

HOXA5 Is Recognized as a Prognostic-Related Biomarker and Promotes Glioma Progression Through Affecting Cell Cycle

Immune Checkpoints: Therapeutic Targets for Pituitary Tumors

Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment

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