scholarly journals Conserved angio-immune subtypes of the cancer microenvironment predict response to immune checkpoint blockade therapy

2021 ◽  
Author(s):  
Madhav Subramanian ◽  
Ashraf Ul Kabir ◽  
Derek A. G. Barisas ◽  
Karen Krchma ◽  
Kyunghee Choi
Keyword(s):  
Immune Checkpoint ◽  
Cell Activity ◽  
Treatment Decision ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
The Cancer Genome Atlas ◽  
Immune Activity ◽  
Treatment Decision Making ◽  
Hematological Tumors ◽  
The One

Tumor microenvironment (TME) shapes the tumor progression and therapy outcome. Particularly, tumor angiogenesis and immunity impact the effect of immune checkpoint blockade (ICB) therapy. Here, we analyzed the transcriptome from 11,069 patients from The Cancer Genome Atlas (TCGA) to assess 91 functional gene sets corresponding to endothelial and T-cell activity. Intriguingly, TME across 30 non-hematological tumors can be classified into three distinct conserved angio-immune subtypes: high angiogenesis with low immune activity, low angiogenesis with high immune activity, and the one in-between. Remarkably, patients displaying TME with poor angiogenic activity with corresponding high immune activity show the most significant responses to ICB therapy in many cancer types. Notably, re-evaluation of the Javelin Renal 101, renal cell carcinoma clinical trial, provided compelling evidence that the baseline angiogenic state is critical in determining responses to checkpoint blockade. This study offers a clear rationale for incorporating baseline angiogenic state for ICB treatment decision-making.

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

2020 ◽  
Author(s):  
Qianhui Xu ◽  
Yuxin Wang ◽  
Wen Huang
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Immune Checkpoint ◽  
Risk Model ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas

Abstract 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.

scholarly journals Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Pancreatic Ductal Adenocarcinoma

2020 ◽  
Author(s):  
Qianhui Xu ◽  
Yuxin Wang ◽  
Wen Huang
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Risk Score ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Cox Regression Analysis

Abstract Background: An increasing body of evidence has suggested that long non-coding RNAs (lncRNAs) can serve as essential regulators in cancer immunity. We aimed to establish a robust immune-associated lncRNA signature for pancreatic ductal adenocarcinoma (PDAC) outcome prediction to enhance prognostic accuracy.Methods: Pancreatic cancer samples were obtained from the The Cancer Genome Atlas (TCGA) project. Immune‐related lncRNAs displaying significant association with overall survival (OS) were screened through univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. The prediction reliability was further estimated in the internal validation set and combination set. Gene set enrichment analysis (GSEA) of the lncRNA model risk score was performed for functional annotation. The correlation between immune checkpoint inhibitors and this signature was examined. Results: 5 immune-related lncRNAs were confirmed to establish five‐immune-related lncRNAs prognostic signature. The constructed risk model showed significant correlation with PDAC OS. The area under the curve (AUC) for this lncRNA model was up to 0.747. This immune‐related lncRNA signature was correlated with disease progression and worse survival and was an independent prognostic biomarker. Our signature mediated chondrocyte development, laminin binding and so forth. This risk score model was associated with immune cell infiltration (i.e., CD4 T cells, etc.,) and immune checkpoint blockade (ICB) immunotherapy‐related molecules (i.e., PDCD1 and CTLA4).Conclusion: The immune‐related lncRNA signature we established possesses latent prognostic value for patients with PDAC and may have the potential to measure the response to ICB immunotherapy, which could guide for immunological treatment in PDAC.

Analysis of Advanced Melanomas Changed from Immune Checkpoint Blockade Therapy to Palliative Care

2018 ◽  
Vol 80 (1) ◽  
pp. 51-55
Author(s):  
Ai KAJITA ◽  
Osamu YAMASAKI ◽  
Tatsuya KAJI ◽  
Hiroshi UMEMURA ◽  
Keiji IWATSUKI
Keyword(s):  
Palliative Care ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain's pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain's disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

Potential immunotherapy for Alzheimer disease and age-related dementia

2019 ◽  
Vol 21 (1) ◽  
pp. 21-25 ◽  
Keyword(s):  
Immune System ◽  
Alzheimer Disease ◽  
Cross Talk ◽  
Immune Checkpoint ◽  
Short Review ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
New Approach ◽  
Age Related ◽  
The Brain

Emerging results support the concept that Alzheimer disease (AD) and age-related dementia are affected by the ability of the immune system to contain the brain’s pathology. Accordingly, well-controlled boosting, rather than suppression of systemic immunity, has been suggested as a new approach to modify disease pathology without directly targeting any of the brain’s disease hallmarks. Here, we provide a short review of the mechanisms orchestrating the cross-talk between the brain and the immune system. We then discuss how immune checkpoint blockade directed against the PD-1/PD-L1 pathways could be developed as an immunotherapeutic approach to combat this disease using a regimen that will address the needs to combat AD.

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