BCL11B regulates MICA/B-mediated immune response by acting as a competitive endogenous RNA

Qian, Mengyao; Geng, Jingwen; Luo, Kaili; Huang, Zheng; Zhang, Qinkai; Zhang, Jianan; Ji, Liying; Wu, Jianmin

doi:10.1038/s41388-019-1083-0

Cited by 8 publications

(11 citation statements)

References 60 publications

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“…BCL11B inactivation in normal thymocytes triggers cell proliferation, TP53 -dependent apoptosis and increases growth of transformed lymphocytes ( 20 ). BCL11B up-regulates NKG2D ligands of the major histocompatibility complex class I-related molecules A and B (MICA and MICB), promotes the anti-tumor response of T- and NK-cells and prevents immune evasion of colon cancer cells ( 21 ). Down-regulation of BCL11B expression inhibits proliferation and induces apoptosis in malignant T-cells ( 22 , 23 ).…”

Section: Discussionmentioning

confidence: 99%

A survival prediction model and nomogram based on immune-related gene expression in chronic lymphocytic leukemia cells

et al. 2022

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IntroductionThere are many different chronic lymphoblastic leukemia (CLL) survival prediction models and scores. But none provide information on expression of immune-related genes in the CLL cells.MethodsWe interrogated data from the Gene Expression Omnibus database (GEO, GSE22762; Number = 151; training) and International Cancer Genome Consortium database (ICGC, CLLE-ES; Number = 491; validation) to develop an immune risk score (IRS) using Least absolute shrinkage and selection operator (LASSO) Cox regression analyses based on expression of immune-related genes in CLL cells. The accuracy of the predicted nomogram we developed using the IRS, Binet stage, and del(17p) cytogenetic data was subsequently assessed using calibration curves.ResultsA survival model based on expression of 5 immune-related genes was constructed. Areas under the curve (AUC) for 1-year survivals were 0.90 (95% confidence interval, 0.78, 0.99) and 0.75 (0.54, 0.87) in the training and validation datasets, respectively. 5-year survivals of low- and high-risk subjects were 89% (83, 95%) vs. 6% (0, 17%; p < 0.001) and 98% (95, 100%) vs. 92% (88, 96%; p < 0.001) in two datasets. The IRS was an independent survival predictor of both datasets. A calibration curve showed good performance of the nomogram. In vitro, the high expression of CDKN2A and SREBF2 in the bone marrow of patients with CLL was verified by immunohistochemistry analysis (IHC), which were associated with poor prognosis and may play an important role in the complex bone marrow immune environment.ConclusionThe IRS is an accurate independent survival predictor with a high C-statistic. A combined nomogram had good survival prediction accuracy in calibration curves. These data demonstrate the potential impact of immune related genes on survival in CLL.

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Section: Discussionmentioning

confidence: 99%

A survival prediction model and nomogram based on immune-related gene expression in chronic lymphocytic leukemia cells

et al. 2022

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“… 30 Mechanism studies revealed that BCL11B prevents cancer immune evasion by acting as a competitive endogenous RNA to upregulate MICA and MICB, which essentially control tumor immune surveillance. 31 On the other hand, the remaining four immune‐related genes are reportedly oncogenic. For instance, CARD11, also known as CARMA1, is mainly expressed in lymphoid tissues and is involved in both adaptive immunity and carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, it is required for the development and activation of mature T cells and participates in the development of invariant natural killer T (iNKT) cells, which play a key role in immune regulation and antitumor responses 30 . Mechanism studies revealed that BCL11B prevents cancer immune evasion by acting as a competitive endogenous RNA to upregulate MICA and MICB, which essentially control tumor immune surveillance 31 . On the other hand, the remaining four immune‐related genes are reportedly oncogenic.…”

Section: Discussionmentioning

confidence: 99%

Construction of ovarian metastasis‐related immune signature predicting prognosis of gastric cancer patients

et al. 2022

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Background Ovarian metastasis (OM) results in poor survival of gastric cancer (GC) patients. While immunotherapy has emerged as a promising approach for late‐stage GC, validated immune‐related prognostic signatures still remain in need. In this study, we constructed an ovarian metastasis‐ and immune‐related prognostic signature (OMIRPS), characterized the molecular and immune features of OMIRPS‐categorized subgroups and predicted their potential response to immunotherapy. Methods Three individual cohorts were used to construct and evaluate OMIRPS: RNA‐seq of matched primary GC and OM from Fudan University Shanghai Cancer Center (FUSCC) (discovery cohort, n = 4), The Cancer Genome Atlas (TCGA) (training cohort, n = 544) and GSE84437 (validation cohort, n = 433). Differentially expressed genes (DEGs) identified between primary GC and OM and immune‐related genes (IRGs) from the ImmPort and InnateDB databases were used to identify immune‐related prognostic hub genes, which were further used to construct OMIRPS by using LASSO regression analysis. Prognosis, molecular characteristics, immune features, and differential immunotherapy efficacy between different OMIRPS subgroups were analyzed. Results Functional analyses of DEGs revealed the significance of immune‐related signatures and pathways in the OM. Immune‐related prognostic hub genes including TNFRSF18 , CARD11 , BCL11B , NRP1 , BNIP3L, and ATF3 were utilized to construct OMIRPS, which was identified as an independent prognostic factor. Comprehensive analyses unveiled the distinctive molecular and immune characteristics of OMIRPS‐high and ‐low subgroup in regard to enriched pathways, mutation rate, tumor mutation burden, microsatellite instability status, infiltrated immune cell, immune exclusion score, and the prediction of immunotherapy efficacy. Additionally, OMIRPS was associated with Immune Subtypes with borderline significance. Conclusions RNA‐seq of paired primary and ovarian metastatic tumors unveiled the significance of immune‐related pathways and tumor immune microenvironment in OM. OMIRPS served as a promising biomarker to predict the prognosis of GC patients and distinguish the molecular features, immune characteristics, and efficacy of immunotherapy between different subgroups.

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“…There are a variety of NKG2D ligands, and the regulatory mechanisms that control their expression vary contextually [57][58][59][60]. NKG2D ligands have been identified only in placental and marsupial mammals [61].…”

Section: Nkg2d Ligandsmentioning

confidence: 99%

Regulation of NKG2D Stress Ligands and Its Relevance in Cancer Progression

Friedman

2022

Cancers

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Under cellular distress, multiple facets of normal homeostatic signaling are altered or disrupted. In the context of the immune landscape, external and internal stressors normally promote the expression of natural killer group 2 member D (NKG2D) ligands that allow for the targeted recognition and killing of cells by NKG2D receptor-bearing effector populations. The presence or absence of NKG2D ligands can heavily influence disease progression and impact the accessibility of immunotherapy options. In cancer, tumor cells are known to have distinct regulatory mechanisms for NKG2D ligands that are directly associated with tumor progression and maintenance. Therefore, understanding the regulation of NKG2D ligands in cancer will allow for targeted therapeutic endeavors aimed at exploiting the stress response pathway. In this review, we summarize the current understanding of regulatory mechanisms controlling the induction and repression of NKG2D ligands in cancer. Additionally, we highlight current therapeutic endeavors targeting NKG2D ligand expression and offer our perspective on considerations to further enhance the field of NKG2D ligand biology.

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BCL11B regulates MICA/B-mediated immune response by acting as a competitive endogenous RNA

Cited by 8 publications

References 60 publications

A survival prediction model and nomogram based on immune-related gene expression in chronic lymphocytic leukemia cells

A survival prediction model and nomogram based on immune-related gene expression in chronic lymphocytic leukemia cells

Construction of ovarian metastasis‐related immune signature predicting prognosis of gastric cancer patients

Regulation of NKG2D Stress Ligands and Its Relevance in Cancer Progression

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