The Role of Long Non-coding RNAs in Immunotherapy Resistance

Zhou, Yuwen; Zhu, Yajuan; Xie, Yu; Ma, Xuelei

doi:10.3389/fonc.2019.01292

Cited by 52 publications

(46 citation statements)

References 70 publications

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“…Akt, protein kinase B; lncRNA, long noncoding RNA; mTOR, mammalian target of rapamycin; NK, natural killer; PI3K, phosphatidylinositol-3-kinase F I G U R E 5 Association between the immune-related long noncoding RNA (lncRNA) signature and tumor immune cell infiltration. (a) Correlation between this signature and macrophages M0, (b) correlation between this signature and T cells follicular helper, (c) correlation between this signature and T cells regulatory (Tregs), (d) correlation between this signature and B cells memory, (e) correlation between this signature and eosinophils, (f) correlation between this signature and neutrophils, (g) correlation between this signature and dendritic cells activated, (h) correlation between this signature and T cells CD4 memory resting, (i) correlation between this signature and macrophages M1, (j) correlation between this signature and Mast cells resting, (k) correlation between this signature and B cells naive, (l) correlation between this signature and T cells gamma delta, (m) correlation between this signature and T cells CD8 biomarkers to provide potential support for clinic management and therapy in cancer (Heward & Lindsay, 2014;Xu et al, 2019;Y. Zhou, Zhu, Xie, & Ma, 2019).…”

Section: Discussionmentioning

confidence: 99%

Immune‐related long noncoding RNA signature for predicting survival and immune checkpoint blockade in hepatocellular carcinoma

Zhang

et al. 2020

Journal Cellular Physiology

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Long noncoding RNAs (lncRNAs) show multiple functions, including immune response. Recently, the immune‐related lncRNAs have been reported in some cancers. We first investigated the immune‐related lncRNA signature as a potential target in hepatocellular carcinoma (HCC) survival. The training set (n = 368) and the independent external validation cohort (n = 115) were used. Immune genes and lncRNAs coexpression were constructed to identify immune‐related lncRNAs. Cox regression analyses were perfumed to establish the immune‐related lncRNA signature. Regulatory roles of this signature on cancer pathways and the immunologic features were investigated. The correlation between immune checkpoint inhibitors and this signature was examined. In this study, the immune‐related lncRNA signature was identified in HCC, which could stratify patients into high‐ and low‐risk groups. This immune‐related lncRNA signature was correlated with disease progression and worse survival and was an independent prognostic biomarker. Our immune‐related lncRNA signature was still a powerful tool in predicting survival in each stratum of age, gender, and tumor stage. This signature mediated cell cycle, glycolysis, DNA repair, mammalian target of rapamycin signaling, and immunologic characteristics (i.e., natural killer cells vs. Th1 cells down, etc). This signature was associated with immune cell infiltration (i.e., macrophages M0, Tregs, CD4 memory T cells, and macrophages M1, etc.,) and immune checkpoint blockade (ICB) immunotherapy‐related molecules (i.e., PD‐L1, PD‐L2, and IDO1). Our findings suggested that the immune‐related lncRNA signature had an important value for survival prediction and may have the potential to measure the response to ICB immunotherapy. This signature may guide the selection of the immunotherapy for HCC.

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Section: Discussionmentioning

confidence: 99%

Immune‐related long noncoding RNA signature for predicting survival and immune checkpoint blockade in hepatocellular carcinoma

Zhang

et al. 2020

Journal Cellular Physiology

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“…Another research showed encouraging potentiality for new clinical management decisions on the basis of epigenetic regulation targeting LncMALAT1, which can coordinate with the immune system [37]. More and more evidences has strongly supported that immune-related lncRNAs may be novel disease biomolecules for cancer clinic treatment and possess valuable prognostic signi cance for survival [38,39]. Several immune-related lncRNA signatures have been explored in some tumors, such as bladder cancer, breast cancer, and colon cancer [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Breast Cancer

Xu¹,

Wang²,

Huang³

2020

Preprint

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Background: There have numerous evidences to support that long non-coding RNAs (lncRNAs) may be crucial parts in cancer immunity. We aimed to establish a novel and robust immune-associated lncRNAs signature to improve prognostic precision in patients with breast cancer(BRCA).Methods: BRCA cases were obtained from the The Cancer Genome Atlas (TCGA) database. Immune‐related lncRNAs presenting significant association with prognosis were screened through stepwise univariate Cox regression and LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, ROC analyses, and proportional hazards model further conducted. The prediction reliability was further estimated in the internal validation set and combination set. Gene set enrichment analysis (GSEA) was applied for functional annotation. The correlation between immune checkpoint inhibitors and this signature was employed. Results: 13 immune-related lncRNAs were systematically identified to establish immune-related lncRNAs predictive prognosis signature. The risk model we built showed significant correlation with BRCA patients’ prognosis. The value of ROC for this lncRNAs model was up to 0.821. This immune‐related lncRNAs signature can serve as an independent prognostic biomolecular factor. Our lncRNAs signature involved in chondrocyte development, endoderm development and so forth. This lncRNAs risk model was associated with tumor immune infiltration (i.e., B cells, Dendritic, Neutrophils, CD8 T cells and CD4 T cells, etc.,) and immune checkpoint blockade (ICB) therapy key molecules (i.e., PDCD1).Conclusion: The immune‐related lncRNA signature we established possesses latent prognostic value for patients with BRCA and may have the capability to predict the clinical outcome of ICB treatment, which could provide guidance for immunological decision in patients with BRCA.

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“…Interestingly, some immune-related lncRNAs regulate immunosuppressive mechanisms leading to immune evasion and resistance to immunotherapy. Some examples include loss of antigen presentation, PD-L1 overexpression, regulation of T-cell exhaustion, and MDSC and Treg differentiation and expansion (Zhou et al, 2019;Zheng et al, 2019).…”

Section: Tumor-extrinsic Factors and Resistance To Pd-l1/pd-1 Blockadmentioning

confidence: 99%

Resistance to PD-L1/PD-1 Blockade Immunotherapy. A Tumor-Intrinsic or Tumor-Extrinsic Phenomenon?

et al. 2020

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Cancer immunotherapies targeting immune checkpoints such as programmed cell-death protein 1 (PD-1) and its ligand programmed cell-death 1 ligand 1 (PD-L1), are revolutionizing cancer treatment and transforming the practice of medical oncology. However, despite all the recent successes of this type of immunotherapies, most patients are still refractory and present either intrinsic resistance or acquired resistance. Either way, this is a major clinical problem and one of the most significant challenges in oncology. Therefore, the identification of biomarkers to predict clinical responses or for patient stratification by probability of response has become a clinical necessity. However, the mechanisms leading to PD-L1/PD-1 blockade resistance are still poorly understood. A deeper understanding of the basic mechanisms underlying resistance to cancer immunotherapies will provide insight for further development of novel strategies designed to overcome resistance and treatment failure. Here we discuss some of the major molecular mechanisms of resistance to PD-L1/PD-1 immune checkpoint blockade and argue whether tumor intrinsic or extrinsic factors constitute main determinants of response and resistance.

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The Role of Long Non-coding RNAs in Immunotherapy Resistance

Cited by 52 publications

References 70 publications

Immune‐related long noncoding RNA signature for predicting survival and immune checkpoint blockade in hepatocellular carcinoma

Immune‐related long noncoding RNA signature for predicting survival and immune checkpoint blockade in hepatocellular carcinoma

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Breast Cancer

Resistance to PD-L1/PD-1 Blockade Immunotherapy. A Tumor-Intrinsic or Tumor-Extrinsic Phenomenon?

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