scholarly journals Cross-platform meta-analysis reveals common matrisome variation associated with tumor genotypes and immunophenotypes in human cancers

2018 ◽  
Author(s):  
Su Bin Lim ◽  
Swee Jin Tan ◽  
Wan-Teck Lim ◽  
Chwee Teck Lim
Keyword(s):  
Immune Cell ◽  
Immune Escape ◽  
Wide Spectrum ◽  
Meta Analysis ◽  
Immune Checkpoints ◽  
Tumor Immune Escape ◽  
Data Resource ◽  
Specific Tumor ◽  
Cross Platform ◽  
Immune Escape Mechanisms

AbstractBackgroundRecent sequencing efforts unveil genomic landscapes of the tumor microenvironment. Yet, little is known about the extent to which matrisome pattern is conserved in progressive tumors across diverse cancer types, and thus its clinical impact remains largely unexplored.FindingsUsing a newly generated, unified data resource, we conducted cross-platform assessment of a measure of altered extra-cellular matrix (ECM) composition and remodeling associated with tumor progression, termed as the matrisome index (TMI). Parallel analyses with TCGA in over 30,000 patient-derived biopsies revealed that TMI is closely associated with mutational load, tumor histopathology, and predictive of patient outcomes. We found an enrichment of specific tumor-infiltrating immune cell populations, signatures predictive of immunotherapy resistance, and several immune checkpoints in tumors with high TMI, suggesting potential role of ECM interaction with immunophenotyes and tumor immune escape mechanisms. Both epithelial cancer cells and carcinoma-associated fibroblasts are potential cellular contributors of such deregulated matrisome.ConclusionsDespite wide spectrum of genetic heterogeneity and dynamic nature, matrisome abnormalities are integral to disease progression. Our resource of a curated compendium of 8,386 genome-wide profiles, molecular and clinical associations, and matrisome-tumor genotype-immunophenotype relationships identify potentially actionable immune targets that may guide personalized immunotherapy.

scholarly journals Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

2020 ◽  
Vol 21 (7) ◽  
pp. 2286 ◽  
Author(s):  
Stefania Raimondo ◽  
Marzia Pucci ◽  
Riccardo Alessandro ◽  
Simona Fontana
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Immune Escape ◽  
Immune Checkpoints ◽  
Cancer Therapies ◽  
Biological Functions ◽  
Hallmarks Of Cancer ◽  
Tumor Immune Escape

The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in regulating immune checkpoints, focusing on the PD-L1/PD-1 axis.

scholarly journals Unveiling the immune infiltrate modulation in cancer and response to immunotherapy by MIXTURE—an enhanced deconvolution method

2020 ◽  
Author(s):  
Elmer A Fernández ◽  
Yamil D Mahmoud ◽  
Florencia Veigas ◽  
Darío Rocha ◽  
Matías Miranda ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Escape ◽  
Intratumor Heterogeneity ◽  
Support Vector ◽  
Tumor Immune Escape ◽  
Immune Infiltrate ◽  
Tumor Biopsies

Abstract The accurate quantification of tumor-infiltrating immune cells turns crucial to uncover their role in tumor immune escape, to determine patient prognosis and to predict response to immune checkpoint blockade. Current state-of-the-art methods that quantify immune cells from tumor biopsies using gene expression data apply computational deconvolution methods that present multicollinearity and estimation errors resulting in the overestimation or underestimation of the diversity of infiltrating immune cells and their quantity. To overcome such limitations, we developed MIXTURE, a new ν-support vector regression-based noise constrained recursive feature selection algorithm based on validated immune cell molecular signatures. MIXTURE provides increased robustness to cell type identification and proportion estimation, outperforms the current methods, and is available to the wider scientific community. We applied MIXTURE to transcriptomic data from tumor biopsies and found relevant novel associations between the components of the immune infiltrate and molecular subtypes, tumor driver biomarkers, tumor mutational burden, microsatellite instability, intratumor heterogeneity, cytolytic score, programmed cell death ligand 1 expression, patients’ survival and response to anti-cytotoxic T-lymphocyte-associated antigen 4 and anti-programmed cell death protein 1 immunotherapy.

scholarly journals Implications of Corticotropin Releasing Factor in Targeted Anticancer Therapy

2010 ◽  
Vol 23 (2) ◽  
pp. 86-90 ◽  
Author(s):  
Byung-Jin Kim ◽  
Harlan P. Jones
Keyword(s):  
Side Effects ◽  
Immune Escape ◽  
Anticancer Therapy ◽  
Corticotropin Releasing Factor ◽  
Antitumor Therapy ◽  
Tumor Immune Escape ◽  
Adverse Side Effects ◽  
Psychological Indicators ◽  
Immune Escape Mechanisms

There is a need to develop novel anticancer therapies that eliminate adverse side effects produced by current treatments. Corticotropin releasing factor (CRF), an endogenous neuroedocrine factor, which typically regulates biological and psychological indicators of stress, has recently been found to be expressed by tumor malignancies. Here, we discuss the implications of CRF as a target for antitumor therapy through regulation of tumor immune escape mechanisms.

scholarly journals The Identification and Validation of Two Heterogenous Subtypes and a Risk Signature Based on Ferroptosis in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zaoqu Liu ◽  
Libo Wang ◽  
Long Liu ◽  
Taoyuan Lu ◽  
Dechao Jiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chromatin Remodeling ◽  
Vascular Invasion ◽  
Immune Escape ◽  
Immune Checkpoints ◽  
Related Risk ◽  
Tumorigenesis And Progression ◽  
Immunosuppressive Cells ◽  
Immune Escape Mechanisms ◽  
Worse Prognosis

BackgroundFerroptosis is essential for tumorigenesis and progression of hepatocellular carcinoma (HCC). The heterogeneity of ferroptosis and its relationship with tumor microenvironment (TME) have still remain elusive.MethodsBased on 74 ferroptosis related genes (FRGs) and 3,933 HCC samples from 32 datasets, we comprehensively explored the heterogenous ferroptosis subtypes. The clinical significance, functional status, immune infiltration, immune escape mechanisms, and genomic alterations of different subtypes were further investigated.ResultsWe identified and validated two heterogeneous ferroptosis subtypes: C1 was metabolismlowimmunityhigh subtype and C2 was metabolismhighimmunitylow subtype. Compared to C2, C1 owned worse prognosis, and C1 tended to occur in the patients with clinical characteristics such as younger, female, advanced stage, higher grade, vascular invasion. C1 and C2 were more sensitive to immunotherapy and sorafenib, respectively. The immune escape mechanisms of C1 might be accumulating more immunosuppressive cells, inhibitory cytokines, and immune checkpoints, while C2 was mainly associated with inferior immunogenicity, defecting in antigen presentation, and lacking leukocytes. In addition, C1 was characterized by BAP1 mutation, MYC amplification, and SCD1 methylation, while C2 was characterized by the significant alterations in cell cycle and chromatin remodeling processes. We also constructed and validated a robust and promising signature termed ferroptosis related risk score (FRRS) for assessing prognosis and immunotherapy.ConclusionWe identified and validated two heterogeneous ferroptosis subtypes and a reliable risk signature which used to assess prognosis and immunotherapy. Our results facilitated the understood of ferroptosis as well as clinical management and precise therapy of HCC.

scholarly journals The role of tumor-derived exosomes in tumor immune escape: A concise review

2020 ◽  
Vol 7 (11) ◽  
pp. 4132-4137
Author(s):  
Nhat Chau Truong ◽  
Thao Nhi Huynh ◽  
Khuong Duy Pham ◽  
Phuc Van Pham
Keyword(s):  
Immune Modulation ◽  
Immune Escape ◽  
Suppressor Cells ◽  
Target Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Immune Escape ◽  
Concise Review ◽  
Viable Cells ◽  
Immune Escape Mechanisms

Exosomes are small vesicles secreted by viable cells into the microenvironment. These vesicles bring various compositions, including lipids, RNAs and proteins, which carry information from producer cells to target cells. Cancer cells also produce exosomes, termed as tumor-derived exosomes (TDEs), which play important roles in immune modulation, angiogenesis and metastasis of tumors. This review summarizes the roles of TDEs in tumor immune escape mechanisms. TDEs affect all kinds of tumor-associated immune cells, including natural killer (NK) cells, dendritic cells (DCs), T and B lymphocytes, and myeloid-derived suppressor cells (MDSCs). Generally, TDEs suppress the immune system to promote tumor immune escape, thereby significantly contributing to tumorigenesis and metastasis.

scholarly journals Immunosuppressive Roles of Galectin-1 in the Tumor Microenvironment

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1398
Author(s):  
Yanyu Huang ◽  
Hsiao-Chi Wang ◽  
Junwei Zhao ◽  
Ming-Heng Wu ◽  
Tsung-Chieh Shih
Keyword(s):  
Tumor Microenvironment ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Human Tumor ◽  
Immune Cell Function ◽  
Tumor Immune Escape ◽  
Cancer Tumor ◽  
And Function

Evasion of immune surveillance is an accepted hallmark of tumor progression. The production of immune suppressive mediators by tumor cells is one of the major mechanisms of tumor immune escape. Galectin-1 (Gal-1), a pivotal immunosuppressive molecule, is expressed by many types of cancer. Tumor-secreted Gal-1 can bind to glycosylated receptors on immune cells and trigger the suppression of immune cell function in the tumor microenvironment, contributing to the immune evasion of tumors. The aim of this review is to summarize the current literature on the expression and function of Gal-1 in the human tumor microenvironment, as well as therapeutics targeting Gal-1.

scholarly journals Comprehensive Molecular Analyses of a Novel Mutational Signature Classification System with Regard to Prognosis, Genomic Alterations, and Immune Landscape in Glioma

2021 ◽  
Vol 8 ◽  
Author(s):  
Zaoqu Liu ◽  
Taoyuan Lu ◽  
Libo Wang ◽  
Long Liu ◽  
Lifeng Li ◽  
...  
Keyword(s):  
Immune Escape ◽  
Molecular Classification ◽  
Idh1 Mutation ◽  
Immune Checkpoints ◽  
Chromosome 1P ◽  
Molecular Features ◽  
Public Datasets ◽  
Carcinogenic Process ◽  
Immunosuppressive Cells ◽  
Immune Escape Mechanisms

Background: Glioma is the most common malignant brain tumor with complex carcinogenic process and poor prognosis. The current molecular classification cannot fully elucidate the molecular diversity of glioma.Methods: Using broad public datasets, we performed cluster analysis based on the mutational signatures and further investigated the multidimensional heterogeneity of the novel glioma molecular subtypes. The clinical significance and immune landscape of four clusters also investigated. The nomogram was developed using the mutational clusters and clinical characteristics.Results: Four heterogenous clusters were identified, termed C1, C2, C3, and C4, respectively. These clusters presented distinct molecular features: C1 was characterized by signature 1, PTEN mutation, chromosome seven amplification and chromosome 10 deletion; C2 was characterized by signature 8 and FLG mutation; C3 was characterized by signature 3 and 13, ATRX and TP53 mutations, and 11p15.1, 11p15.5, and 13q14.2 deletions; and C4 was characterized by signature 16, IDH1 mutation and chromosome 1p and 19q deletions. These clusters also varied in biological functions and immune status. We underlined the potential immune escape mechanisms: abundant stromal and immunosuppressive cells infiltration and immune checkpoints (ICPs) blockade in C1; lack of immune cells, low immunogenicity and antigen presentation defect in C2 and C4; and ICPs blockade in C3. Moreover, C4 possessed a better prognosis, and C1 and C3 were more likely to benefit from immunotherapy. A nomogram with excellent performance was also developed for assessing the prognosis of patients with glioma.Conclusion: Our results can enhance the mastery of molecular features and facilitate the precise treatment and clinical management of glioma.

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