Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma DOI Creative Commons
Chen Chen, Zehua Wang, Yi Ding

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 10, 2023

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and third leading cause of tumor-related mortality worldwide. In recent years, emergency immune checkpoint inhibitor (ICI) has revolutionized management HCC. Especially, combination atezolizumab (anti-PD1) bevacizumab (anti-VEGF) been approved by FDA as first-line treatment for advanced Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing drug resistance frequent recurrence. The tumor microenvironment (TME) complex structured mixture characterized abnormal angiogenesis, chronic inflammation, dysregulated extracellular matrix (ECM) remodeling, collectively contributing immunosuppressive milieu that turn prompts proliferation, invasion, metastasis. coexists interacts with various cells maintain development It widely accepted dysfunctional tumor-immune ecosystem can lead failure surveillance. TME an external evasion consisting 1) cells; 2) co-inhibitory signals; 3) soluble cytokines signaling cascades; 4) metabolically hostile microenvironment; 5) gut microbiota affects microenvironment. Importantly, effectiveness immunotherapy largely depends on (TIME). Also, metabolism profoundly affect Understanding how progression will contribute better preventing HCC-specific overcoming already developed therapies. this review, we mainly introduce underlying role microenvironment, describe dynamic interaction microbiome, propose therapeutic strategies manipulate favor more effective immunotherapy.

Language: Английский

Pattern recognition receptors in health and diseases DOI Creative Commons
Danyang Li, Minghua Wu

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Aug. 4, 2021

Abstract Pattern recognition receptors (PRRs) are a class of that can directly recognize the specific molecular structures on surface pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity immunity. Through binding ligands, produce anti-infection, antitumor, other immunoprotective effects. Most in innate immune system vertebrates be classified into following five types based protein domain homology: Toll-like (TLRs), nucleotide oligomerization (NOD)-like (NLRs), retinoic acid-inducible gene-I (RIG-I)-like (RLRs), C-type lectin (CLRs), absent melanoma-2 (AIM2)-like (ALRs). basically composed ligand domains, intermediate effector domains. bind their respective ligands recruit adaptor molecules with same structure through initiating downstream signaling pathways to exert In recent years, increased researches have greatly promoted understanding different provided ideas for treatment immune-related diseases even tumors. This review describes detail history, structural characteristics, mechanism, pathway, related disease, new drugs clinical trials therapy PRRs, discusses significance research pattern mechanism PRR-related diseases.

Language: Английский

Citations

1059
Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma DOI Creative Commons
Zhigang Ren, Ang Li, Jianwen Jiang

et al.

Gut, Journal Year: 2018, Volume and Issue: 68(6), P. 1014 - 1023

Published: July 25, 2018

Objective To characterise gut microbiome in patients with hepatocellular carcinoma (HCC) and evaluate the potential of as non-invasive biomarkers for HCC. Design We collected 486 faecal samples from East China, Central China Northwest prospectively finally 419 completed Miseq sequencing. characterised microbiome, identified microbial markers constructed HCC classifier 75 early HCC, 40 cirrhosis healthy controls. validated results 56 controls, 30 45 advanced further verified diagnosis 18 Xinjiang 80 Zhengzhou. Results Faecal diversity was increased to cirrhosis. Phylum Actinobacteria versus Correspondingly, 13 genera including Gemmiger Parabacteroides were enriched Butyrate-producing decreased, while producing-lipopolysaccharide The optimal through a fivefold cross-validation on random forest model achieved an area under curve 80.64% between 105 non-HCC samples. Notably, strong even Importantly, successfully cross-region validation China. Conclusions This study is first report successful establishment Gut microbiota-targeted represent tools

Language: Английский

Citations

596
Mechanisms of Fibrosis Development in Nonalcoholic Steatohepatitis DOI
Robert F. Schwabe, Ira Tabas, Utpal B. Pajvani

et al.

Gastroenterology, Journal Year: 2020, Volume and Issue: 158(7), P. 1913 - 1928

Published: Feb. 8, 2020

Language: Английский

Citations

490
Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets DOI
Yoon Mee Yang, Sohee Kim, Ekihiro Seki

et al.

Seminars in Liver Disease, Journal Year: 2019, Volume and Issue: 39(01), P. 026 - 042

Published: Jan. 17, 2019

Abstract Hepatocellular carcinoma (HCC) is associated with chronic inflammation and fibrosis arising from different etiologies, including hepatitis B C alcoholic nonalcoholic fatty liver diseases. The inflammatory cytokines tumor necrosis factor-α interleukin-6 their downstream targets nuclear factor kappa (NF-κB), c-Jun N-terminal kinase (JNK), signal transducer activator of transcription 3 drive inflammation-associated HCC. Further, while adaptive immunity promotes immune surveillance to eradicate early HCC, cells, such as CD8+ T Th17 can also stimulate HCC development. Thus, the role hepatic system in development a highly complex topic. This review highlights cytokine signals, NF-κB, JNK, innate immunity, stellate cells discusses whether these pathways could be therapeutic targets. authors will discuss cholangiocarcinoma metastasis because biliary tumor-associated stroma are essential for primary tumor-derived mediators promote formation “premetastasis niche” liver.

Language: Английский

Citations

341
The liver cancer immune microenvironment: Therapeutic implications for hepatocellular carcinoma DOI Open Access
Romain Donné, Amaia Lujambio

Hepatology, Journal Year: 2022, Volume and Issue: 77(5), P. 1773 - 1796

Published: Aug. 22, 2022

The liver is the sixth most common site of primary cancer in humans and fourth leading cause cancer‐related death world. Hepatocellular carcinoma (HCC) accounts for 90% cancers. HCC a prevalent disease with progression that modulated by immune system. Half patients receive systemic therapies, traditionally sorafenib or lenvatinib, as first‐line therapy. In last few years, immune‐checkpoint inhibitors (ICIs) have revolutionized therapy gained an increased interest treatment HCC. 2020, combination atezolizumab (anti‐programmed death‐ligand 1) bevacizumab (anti–vascular endothelial growth factor) improved overall survival over sorafenib, resulting Food Drug Administration (FDA) approval advanced Despite these major advances, better molecular cellular characterization tumor microenvironment still needed because it has crucial role development Inflamed (hot) noninflamed (cold) tumors genomic signatures been associated response to ICIs. However, there are no additional biomarkers guide clinical decision‐making. Other immune‐targeting strategies, such adoptive T‐cell transfer, vaccination, virotherapy, currently under development. This review provides overview on microenvironment, different players, current available immunotherapies, potential immunotherapy modalities.

Language: Английский

Citations

327
Contribution of the Intestinal Microbiome and Gut Barrier to Hepatic Disorders DOI Open Access
Daniel M. Chopyk, Arash Grakoui

Gastroenterology, Journal Year: 2020, Volume and Issue: 159(3), P. 849 - 863

Published: June 20, 2020

Language: Английский

Citations

320
Gut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer DOI
Patrice D. Cani, Bénédicte F. Jordan

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2018, Volume and Issue: 15(11), P. 671 - 682

Published: May 29, 2018

Language: Английский

Citations

318
Gut microbiome in HCC – Mechanisms, diagnosis and therapy DOI Open Access
Robert F. Schwabe, Tim F. Greten

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 72(2), P. 230 - 238

Published: Jan. 15, 2020

Language: Английский

Citations

275
Role of nonresolving inflammation in hepatocellular carcinoma development and progression DOI Creative Commons

Le–Xing Yu,

Ling Yan, Hongyang Wang

et al.

npj Precision Oncology, Journal Year: 2018, Volume and Issue: 2(1)

Published: Feb. 19, 2018

Abstract Hepatocellular carcinoma (HCC) has become a leading cause of cancer-related death, making the elucidation its underlying mechanisms an urgent priority. Inflammation is adaptive response to infection and tissue injury under strict regulations. When host regulatory machine runs out control, nonresolving inflammation occurs. Nonresolving recognized hallmark cancer that substantially contributes development progression HCC. The HCC-associated can be initiated propagated by extrinsic pathways through activation pattern-recognition receptors (PRRs) pathogen-associated molecule patterns (PAMPs) derived from gut microflora or damage-associated (DAMPs) released dying liver cells. also orchestrated tumor itself secreting factors recruit inflammatory cells favoring buildup microenvironment. Accumulating datas human mouse models showed promotes HCC promoting proliferative survival signaling, inducing angiogenesis, evading immune surveillance, supporting stem cells, activating invasion metastasis as well genomic instability. Targeting may represent promising avenue for treatment. Some inhibitors targeting have been developed different stages clinical trials, one (sorafenib) approved FDA. However, most data were obtained animal models, there big difference between it challenging on successful translation bench bedside.

Language: Английский

Citations

267
Fecal microbiota transplantation in cancer management: Current status and perspectives DOI Creative Commons
Danfeng Chen, Jingyi Wu, Duochen Jin

et al.

International Journal of Cancer, Journal Year: 2018, Volume and Issue: 145(8), P. 2021 - 2031

Published: Nov. 20, 2018

The human gut is home to a large and diverse microbial community, comprising about 1,000 bacterial species. microbiota exists in symbiotic relationship with its host, playing decisive role the host's nutrition, immunity metabolism. Accumulating studies have revealed associations between dysbiosis or some special bacteria various cancers. Emerging data suggest that can modulate effectiveness of cancer therapies, especially immunotherapy. Manipulating populations therapeutic intent has become hot topic research, most dramatic manipulation refers fecal transplantation (FMT) from healthy individuals patients. FMT demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) it highly recommended for treatment recurrent refractory CDI. Lately, interest growing potential other diseases, including We briefly reviewed current researches link cancer, then summarized recent preclinical evidence indicate management as well cancer‐treatment associated complications. also presented rationale such reconstruction intestinal microbiota, amelioration bile acid metabolism, modulation immunotherapy efficacy. This article would help better understand this new approach patients by targeting microbiota.

Language: Английский

Citations

258