Multi-omics Analysis of Microenvironment Characteristics and Immune Escape Mechanisms of Hepatocellular Carcinoma

2019 ◽  
Author(s):  
Wenli Lib ◽  
Huimei Wang ◽  
Zhanzhong Ma ◽  
Jian Zhang ◽  
Wen Ou-yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Escape ◽  
Omics Analysis ◽  
Immune Escape Mechanisms

scholarly journals Multi-omics Analysis of Microenvironment Characteristics and Immune Escape Mechanisms of Hepatocellular Carcinoma

2019 ◽  
Vol 9 ◽  
Author(s):  
Wenli Li ◽  
Huimei Wang ◽  
Zhanzhong Ma ◽  
Jian Zhang ◽  
Wen Ou-yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Escape ◽  
Omics Analysis ◽  
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 A novel immune classification reveals distinct immune escape mechanism and genomic alterations: implications for immunotherapy in hepatocellular carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zaoqu Liu ◽  
Yuyuan Zhang ◽  
Chengcheng Shi ◽  
Xueliang Zhou ◽  
Kaihao Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Immune Escape ◽  
Pi3k Pathway ◽  
Single Patient ◽  
Genomic Alterations ◽  
Time Index ◽  
Immunosuppressive Cells ◽  
Immune Escape Mechanisms ◽  
Geo Database

Abstract Background The tumor immunological microenvironment (TIME) has a prominent impact on prognosis and immunotherapy. However, the heterogeneous TIME and the mechanisms by which TIME affects immunotherapy have not been elucidated in hepatocellular carcinoma (HCC). Methods A total of 2195 eligible HCC patients from TCGA and GEO database were collected. We comprehensively explored the different heterogeneous TIME phenotypes and its clinical significance. The potential immune escape mechanisms and what genomic alterations may drive the formation of different phenotypes were further investigated. Results We identified three phenotypes in HCC: TIME-1, the “immune-deficiency” phenotype, with immune cell depletion and proliferation; TIME-2, the “immune-suppressed” phenotype, with enrichment of immunosuppressive cells; TIME-3, the “immune-activated phenotype”, with abundant leukocytes infiltration and immune activation. The prognosis and sensitivity to both sorafenib and immunotherapy differed among the three phenotypes. We also underlined the potential immune escape mechanisms: lack of leukocytes and defective tumor antigen presentation capacity in TIME-1, increased immunosuppressive cells in TIME-2, and rich in immunoinhibitory molecules in TIME-3. The different phenotypes also demonstrated specific genomic events: TIME-1 characterized by TP53, CDKN2A, CTNNB1, AXIN1 and FOXD4 alterations; TIME-2 characterized by significant alteration patterns in the PI3K pathway; TIME-3 characterized by ARID1A mutation. Besides, the TIME index (TI) was proposed to quantify TIME infiltration pattern, and it was a superior prognostic and immunotherapy predictor. A pipeline was developed to classify single patient into one of these three subtypes and calculated the TI. Conclusions We identified three TIME phenotypes with different clinical outcomes, immune escape mechanisms and genomic alterations in HCC, which could present strategies for improving the efficacy of immunotherapy. TI as a novel prognostic and immunotherapeutic signature that could guide personalized immunotherapy and clinical management of HCC.

scholarly journals A Novel Immune Classification Reveals Distinct Immune Escape Mechanism and Genomic Alterations: Implications for Immunotherapy in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zaoqu Liu ◽  
Yuyuan Zhang ◽  
Chengcheng Shi ◽  
Xueliang Zhou ◽  
Kaihao Xu ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Immune Escape ◽  
Pi3k Pathway ◽  
Genomic Alterations ◽  
Time Index ◽  
Immunosuppressive Cells ◽  
Immune Escape Mechanisms ◽  
Geo Database

Abstract BackgroundThe tumor immunological microenvironment (TIME) has a prominent impact on prognosis and immunotherapy. However, the heterogeneous TIME and the mechanisms by which TIME affects immunotherapy have not been elucidated in hepatocellular carcinoma (HCC).MethodsA total of 2195 eligible HCC patients from TCGA and GEO database were collected. We comprehensively explored the different heterogeneous TIME phenotypes and its clinical significance. The potential immune escape mechanisms and what genomic alterations may drive the formation of different phenotypes were further investigated.ResultsWe identified three phenotypes in HCC: TIME-1, the “immune-deficiency” phenotype, with immune cell depletion and proliferation; TIME-2, the “immune-suppressed” phenotype, with being in immunosuppressive states; TIME-3, the “immune-activated phenotype”, with abundant leukocytes infiltration and immune activation. The prognosis and sensitivity to both sorafenib and immunotherapy differed among the three phenotypes. We also underlined the potential immune escape mechanisms: lack of leukocytes and defective tumor antigen presentation capacity in TIME-1, increased immunosuppressive cells in TIME-2, and rich in immunoinhibitory molecules in TIME-3. The different phenotypes also demonstrated specific genomic events: TIME-1 characterized by TP53, CDKN2A, CTNNB1, AXIN1 and FOXD4 alterations; TIME-2 characterized by significant alteration patterns in the PI3K pathway; TIME-3 characterized by ARID1A mutation. Besides, the TIME index (TI) was proposed to quantify TIME infiltration pattern, and it was a superior prognostic and immunotherapy predictor. ConclusionsWe identified three TIME phenotypes with different clinical outcomes, immune escape mechanisms and genomic alterations in HCC, which could present strategies for improving the efficacy of immunotherapy. TI as a novel prognostic and immunotherapeutic signature that could guide personalized immunotherapy and clinical management of HCC.

scholarly journals A Novel Immune Classification Reveals Distinct Immune Escape Mechanism and Genomic Alterations: Implications for Immunotherapy in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zaoqu Liu ◽  
Yuyuan Zhang ◽  
Chengcheng Shi ◽  
Xueliang Zhou ◽  
Kaihao Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Immune Escape ◽  
Pi3k Pathway ◽  
Single Patient ◽  
Genomic Alterations ◽  
Time Index ◽  
Immunosuppressive Cells ◽  
Immune Escape Mechanisms ◽  
Geo Database

Abstract Background: The tumor immunological microenvironment (TIME) has a prominent impact on prognosis and immunotherapy. However, the heterogeneous TIME and the mechanisms by which TIME affects immunotherapy have not been elucidated in hepatocellular carcinoma (HCC).Methods: A total of 2195 eligible HCC patients from TCGA and GEO database were collected. We comprehensively explored the different heterogeneous TIME phenotypes and its clinical significance. The potential immune escape mechanisms and what genomic alterations may drive the formation of different phenotypes were further investigated.Results: We identified three phenotypes in HCC: TIME-1, the “immune-deficiency” phenotype, with immune cell depletion and proliferation; TIME-2, the “immune-suppressed” phenotype, with being in immunosuppressive states; TIME-3, the “immune-activated phenotype”, with abundant leukocytes infiltration and immune activation. The prognosis and sensitivity to both sorafenib and immunotherapy differed among the three phenotypes. We also underlined the potential immune escape mechanisms: lack of leukocytes and defective tumor antigen presentation capacity in TIME-1, increased immunosuppressive cells in TIME-2, and rich in immunoinhibitory molecules in TIME-3. The different phenotypes also demonstrated specific genomic events: TIME-1 characterized by TP53, CDKN2A, CTNNB1, AXIN1 and FOXD4 alterations; TIME-2 characterized by significant alteration patterns in the PI3K pathway; TIME-3 characterized by ARID1A mutation. Besides, the TIME index (TI) was proposed to quantify TIME infiltration pattern, and it was a superior prognostic and immunotherapy predictor. A pipeline was developed to classify single patient into one of these three subtypes and calculated the TI. Conclusions: We identified three TIME phenotypes with different clinical outcomes, immune escape mechanisms and genomic alterations in HCC, which could present strategies for improving the efficacy of immunotherapy. TI as a novel prognostic and immunotherapeutic signature that could guide personalized immunotherapy and clinical management of HCC.

The association between hepatitis B virus mutations and the risk of liver disease and hepatocellular carcinoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Hassan Akrami ◽  
Mohammad Rafiee Monjezi ◽  
Shahrzad Ilbeigi ◽  
Farshid Amiri ◽  
Mohammad Reza Fattahi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Vaccine Failure ◽  
Occult Hbv Infection ◽  
Occult Hbv ◽  
B Virus ◽  
The World

: Hepatitis B virus [HBV], the best-described hepadnavirus, distributed all around the world and may lead to chronic and acute liver disease, cirrhosis, and hepatocellular carcinoma. Despite the advancement in treatment against HBV, an error-prone reverse transcriptase which is require for HBV replication as well as host immune pressure lead to constant evolution and emergence of genotypes, sub-genotypes and mutant viruses; so, HBV will be remained as a major healthcare problem around the world. This review article mainly focuses on the HBV mutations which correlated to occult HBV infection, Immune scape, vaccine failure and eventually liver cirrhosis and HCC. Current study indicated that preS/S region mutations are related to vaccine failure, immune escape, occult HBV infection and the occurrence of HCC. Whereas, P region Mutations may lead to drug resistance to NA antivirals. PreC/C region mutations are associated to HBeAg negativity, immune escape, and persistent hepatitis. Moreover, X region Mutations play an important role in HCC development.

Translational Research in Cutaneous Melanoma: New Therapeutic Perspectives

2018 ◽  
Vol 18 (2) ◽  
pp. 166-181 ◽  
Author(s):  
Antonio Marra ◽  
Cristina R. Ferrone ◽  
Celeste Fusciello ◽  
Giosue Scognamiglio ◽  
Soldano Ferrone ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Poor Prognosis ◽  
Immune Escape ◽  
Checkpoint Inhibitor ◽  
Predictive Biomarkers ◽  
Driver Mutations ◽  
Targeted Agents ◽  
Therapeutic Approaches ◽  
Aggressive Form ◽  
Immune Escape Mechanisms

Melanoma is an aggressive form of skin cancer characterized by poor prognosis and high mortality. The development of targeted agents based on the discovery of driver mutations as well as the implementation of checkpoint inhibitor-based immunotherapy represents a major breakthrough in the treatment of metastatic melanoma. However, in both cases the development of drug resistance and immune escape mechanisms as well as the lack of predictive biomarkers limits their extraordinary clinical efficacy. In this article, we summarize the available therapeutic options for patients with metastatic melanoma, outline the mechanisms implicated in the resistance to both targeted agents and immunotherapy, discuss potential predictive biomarkers and outline future therapeutic approaches under investigation.

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