MHC class I dysfunction of glioma stem cells escapes from CTL-mediated immune response via activation of Wnt/β-catenin signaling pathway

Yang, Wei; Li, Yanyan; Gao, Ruoling; Xiu, Zenghe; Sun, Ting

doi:10.1038/s41388-019-1045-6

Cited by 75 publications

(69 citation statements)

References 32 publications

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“…Finally, oncogenes c-and n-MYC have both been associated with MHC-I downregulation [186,187,203]. N-MYC has been shown to decrease MHC-I expression in rat neuroblastoma cell lines through the inhibition of the NFkB transcription factor p50 [203].…”

Section: Well-known Oncogenic Pathways Affect Mhc-i Expressionmentioning

confidence: 99%

MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy

Cornel

Mimpen

Nierkens

2020

Cancers

241

203

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In recent years, major advances have been made in cancer immunotherapy. This has led to significant improvement in prognosis of cancer patients, especially in the hematological setting. Nonetheless, translation of these successes to solid tumors was found difficult. One major mechanism through which solid tumors can avoid anti-tumor immunity is the downregulation of major histocompatibility complex class I (MHC-I), which causes reduced recognition by- and cytotoxicity of CD8+ T-cells. Downregulation of MHC-I has been described in 40–90% of human tumors, often correlating with worse prognosis. Epigenetic and (post-)transcriptional dysregulations relevant in the stabilization of NFkB, IRFs, and NLRC5 are often responsible for MHC-I downregulation in cancer. The intrinsic reversible nature of these dysregulations provides an opportunity to restore MHC-I expression and facilitate adaptive anti-tumor immunity. In this review, we provide an overview of the mechanisms underlying reversible MHC-I downregulation and describe potential strategies to counteract this reduction in MHC-I antigen presentation in cancer.

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Section: Well-known Oncogenic Pathways Affect Mhc-i Expressionmentioning

confidence: 99%

MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy

Cornel

Mimpen

Nierkens

2020

Cancers

241

203

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“…Vorinostat, also known as SAHA, in combination with mithramycin A, a Sp1 inhibitor, reverses the histone hypoacetylation which causes APM gene silencing in Merkel cell carcinoma [ 241 ]. In addition, vorinostat promotes tumor cell recognition by CTLs in glioma cells [ 242 , 243 ]. In diffuse large B-cell lymphoma, the HDAC class I inhibitor OKI-179 reverts down-regulation of HLA class I derived peptide complex, a typical feature of this hematological cancer [ 230 ].…”

Section: Restoring Hla Class I Expression As a Novel Therapeutic Smentioning

confidence: 99%

Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients

Sabbatino

Liguori

Polcaro

et al. 2020

IJMS

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Recent advances in cancer immunotherapy have clearly shown that checkpoint-based immunotherapy is effective in a small subgroup of cancer patients. However, no effective predictive biomarker has been identified so far. The major histocompatibility complex, better known in humans as human leukocyte antigen (HLA), is a very polymorphic gene complex consisting of more than 200 genes. It has a crucial role in activating an appropriate host immune response against pathogens and tumor cells by discriminating self and non-self peptides. Several lines of evidence have shown that down-regulation of expression of HLA class I antigen derived peptide complexes by cancer cells is a mechanism of tumor immune escape and is often associated to poor prognosis in cancer patients. In addition, it has also been shown that HLA class I and II antigen expression, as well as defects in the antigen processing machinery complex, may predict tumor responses in cancer immunotherapy. Nevertheless, the role of HLA in predicting tumor responses to checkpoint-based immunotherapy is still debated. In this review, firstly, we will describe the structure and function of the HLA system. Secondly, we will summarize the HLA defects and their clinical significance in cancer patients. Thirdly, we will review the potential role of the HLA as a predictive biomarker for checkpoint-based immunotherapy in cancer patients. Lastly, we will discuss the potential strategies that may restore HLA function to implement novel therapeutic strategies in cancer patients.

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“…GSCs GL261s, and cells were used as GSCs after identification. All cells are isolated, cultured and identified as previously described 27 .…”

Section: Primary Cell Culture Of Human Gscs and Cell Linesmentioning

confidence: 99%

Bip inhibition in glioma stem cells promotes radiation-induced immunogenic cell death

Yang

Xiu

et al. 2020

Cell Death Dis

Self Cite

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Tumor regression in sites distant to the irradiated field are thought to be associated with emission of damage-associated molecular patterns (DAMPs) molecules and generation of immunogenic cell death (ICD). Glioma stem cells (GSCs) are resistant to high doses of radiation, and ultimately select the outgrowth of a more aggressive tumor. This study showed high-dose IR triggered fewer DAMPs molecules exposure and release in GSCs comparing to matched non-GSCs. Downregulation of binding immunoglobulin protein (Bip) promoted IR-mediated endoplasmic reticulum stress to generate DAMPs molecules by PERK and IRE1-α phosphorylation, and increased dendritic cells mature and effector T lymphocytes activation. GSCs treated with Bip knockdown and IR efficiently prevented tumor generation, and reduced post-radiotherapy tumor recurrence. These data suggest that Bip plays a critical role in inhibition of IR-induced ICD in GSCs, and Bip inhibition may be a promising strategy on adjuvant therapy by ameliorating tumor immune microenvironment.

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MHC class I dysfunction of glioma stem cells escapes from CTL-mediated immune response via activation of Wnt/β-catenin signaling pathway

Cited by 75 publications

References 32 publications

MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy

MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy

Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients

Bip inhibition in glioma stem cells promotes radiation-induced immunogenic cell death

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