Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma DOI Creative Commons

Ruipeng Zheng,

Guoqiang Wang, Zhiqiang Pang

et al.

Cancer Medicine, Journal Year: 2020, Volume and Issue: 9(12), P. 4232 - 4250

Published: April 12, 2020

Abstract Background Gut microbiota (GM) of patients with liver cancer is disordered, and syet no study reported the GM distribution cirrhosis‐induced HCC (LC‐HCC) nonliver (NLC‐HCC). In this study, we aimed to characterize gut dysbiosis LC‐HCC NLC‐HCC elucidate role in pathogenesis HCC. Methods A consecutive series fecal samples hepatitis (24 patients), cirrhosis (75 patients: 35 infected by HBV, 25 HCV, 15 alcoholic disease), healthy controls (20 patients) were obtained sequenced on Illumina Hiseq platform. The group contains 52 23 NLC‐HCC. Bioinformatic analysis intestinal was performed QIIME MicrobiomeAnalyst. Results Alpha‐diversity showed that microbial diversity significantly decreased LC group, there significant differences 3 phyla 27 genera vs other groups (the healthy, hepatitis, groups). Beta‐diversity large between others. increased from Characterizing NLC‐HCC, found rather than Thirteen discovered be associated tumor size Three biomarkers ( Enterococcus , Limnobacter Phyllobacterium ) could used for precision diagnosis. We also HBV infection, HCV or ALD (alcoholic disease) not Conclusion Our results suggest disorders are more common LC‐HCC. butyrate‐producing decreased, while producing‐lipopolysaccharide (LPS) patients. Further studies may achieve early diagnosis new therapeutic approaches

Language: Английский

Immunotherapies for hepatocellular carcinoma DOI
Josep M. Llovet, Florian Castet, Mathias Heikenwälder

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(3), P. 151 - 172

Published: Nov. 11, 2021

Language: Английский

Citations

1170
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
Cancer therapy with iron oxide nanoparticles: Agents of thermal and immune therapies DOI Creative Commons

Frederik Soetaert,

Preethi Korangath, David Serantes

et al.

Advanced Drug Delivery Reviews, Journal Year: 2020, Volume and Issue: 163-164, P. 65 - 83

Published: Jan. 1, 2020

Significant research and preclinical investment in cancer nanomedicine has produced several products, which have improved care. Nevertheless, there exists a perception that 'has not lived up to its promise' because the number of approved products their clinical performance are modest. Many these analyses do consider long history many developed from iron oxide nanoparticles. Iron nanoparticles enjoyed use for about nine decades demonstrating safety, considerable utility versatility. FDA-approved applications include diagnosis, hyperthermia therapy, deficiency anemia. For nanomedicine, this wealth experience is invaluable provide key lessons highlight pitfalls pursuit nanotechnology-based therapeutics. We review with systemic liposomal drug delivery parenteral therapy anemia (IDA) note success injectable exploits inherent interaction between (innate) immune system, designers seek avoid. Magnetic fluid hyperthermia, harnesses magnetic hysteresis heating treating humans only Despite successful demonstration enhance overall survival trials, thermal medicine struggles establish presence. physical biological attributes approach, suggest reasons barriers acceptance. Finally, despite extensive new exciting points surprising immune-modulating potential. Recent data demonstrate interactions cells can induce anti-tumor responses. These present opportunities explore additional venerable technology. Clinical poignant case studies opportunities, complexities, challenges nanomedicine. They also illustrate need revised paradigms multidisciplinary approaches develop translate nanomedicines into

Language: Английский

Citations

322
Gut microbiome, liver immunology, and liver diseases DOI Open Access
Rui Wang, Ruqi Tang, Bo Li

et al.

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 18(1), P. 4 - 17

Published: Dec. 14, 2020

Language: Английский

Citations

303
Global Epidemiology and Genetics of Hepatocellular Carcinoma DOI

Ming Ren Toh,

Evelyn Wong, Sunny H. Wong

et al.

Gastroenterology, Journal Year: 2023, Volume and Issue: 164(5), P. 766 - 782

Published: Feb. 2, 2023

Language: Английский

Citations

290
Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors DOI Creative Commons
Daniel Q. Huang, Philippe Mathurin, Helena Cortez‐Pinto

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2022, Volume and Issue: 20(1), P. 37 - 49

Published: Oct. 18, 2022

Heavy alcohol consumption is a major cause of morbidity and mortality. Globally, per-capita rose from 5.5 litres in 2005 to 6.4 2016 projected increase further 7.6 2030. In 2019, an estimated 25% global cirrhosis deaths were associated with alcohol. The age-standardized death rate (ASDR) alcohol-associated was 4.5 per 100,000 population, the highest lowest ASDR Africa Western Pacific, respectively. annual incidence hepatocellular carcinoma (HCC) among patients ranged 0.9% 5.6%. Alcohol approximately one-fifth HCC-related 2019. Between 2012 2017, for declined, but liver cancer increased. Measures are required curb heavy reduce burden HCC. Degree intake, sex, older age, obesity, type 2 diabetes mellitus, gut microbial dysbiosis genetic variants key factors development this Review, we discuss epidemiology, projections risk

Language: Английский

Citations

277
Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers DOI Creative Commons

Jinzhu Mao,

Dongxu Wang, Junyu Long

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2021, Volume and Issue: 9(12), P. e003334 - e003334

Published: Dec. 1, 2021

The gut microbiome is associated with the response to immunotherapy for different cancers. However, impact of on hepatobiliary cancers receiving remains unknown. This study aims investigate relationship between and clinical anti-programmed cell death protein 1 (PD-1) in patients advanced cancers.Patients unresectable hepatocellular carcinoma or biliary tract who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples collected before during anti-PD-1 treatment analyzed metagenomic sequencing. Significantly differentially enriched taxa prognosis identified. Kyoto Encyclopedia Genes Genomes database MetaCyc further applied annotate explore potential mechanism influencing cancer immunotherapy.In total, 65 included this study. Seventy-four significantly benefit (CBR) group 40 non-clinical (NCB) group. Among these taxa, higher abundance Lachnospiraceae bacterium-GAM79 Alistipes sp Marseille-P5997, which CBR group, achieved longer progression-free survival (PFS) overall (OS) than lower abundance. Higher Ruminococcus calidus Erysipelotichaceae bacterium-GAM147 was also observed better PFS. In contrast, worse PFS OS found Veillonellaceae, NCB Functional annotation indicated that energy metabolism while amino acid metabolism, may modulate addition, immunotherapy-related adverse events affected by diversity relative abundance.We demonstrate Taxonomic signatures responders are effective biomarkers predict immunotherapy, might provide a new therapeutic target immunotherapy.

Language: Английский

Citations

188
Gut Microbiome Directs Hepatocytes to Recruit MDSCs and Promote Cholangiocarcinoma DOI Open Access

Qianfei Zhang,

Chi Ma,

Yi Duan

et al.

Cancer Discovery, Journal Year: 2020, Volume and Issue: 11(5), P. 1248 - 1267

Published: Dec. 15, 2020

Gut dysbiosis is commonly observed in patients with cirrhosis and chronic gastrointestinal disorders; however, its effect on antitumor immunity the liver largely unknown. Here we studied how gut microbiome affects cholangiocarcinoma. Primary sclerosing cholangitis (PSC) or colitis, two known risk factors for cholangiocarcinoma which promote tumor development mice, caused an accumulation of CXCR2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). A decrease barrier function mice PSC colitis allowed gut-derived bacteria lipopolysaccharide to appear induced CXCL1 expression hepatocytes through a TLR4-dependent mechanism PMN-MDSCs. In contrast, neomycin treatment blocked PMN-MDSC inhibited growth even absence disease colitis. Our study demonstrates that controls form immunosuppressive environment by increasing PMN-MDSCs cancer. SIGNIFICANCE: MDSCs have been shown be tumors suppress immunity. show can control context benign colitis.See related commentary Chagani Kwong, p. 1014.This article highlighted This Issue feature, 995.

Language: Английский

Citations

176
Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment DOI Creative Commons
Kai Markus Schneider, Antje Mohs, Wenfang Gui

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 8, 2022

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and therapeutic options for advanced HCC are limited. Here, we observe that intestinal dysbiosis affects antitumor immune surveillance drives liver disease progression towards cancer. Dysbiotic microbiota, as seen in Nlrp6

Language: Английский

Citations

135
Gut microbiota influence tumor development and Alter interactions with the human immune system DOI Creative Commons
Yanshan Ge, Xinhui Wang,

Yali Guo

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: Jan. 25, 2021

Abstract Recent scientific advances have greatly enhanced our understanding of the complex link between gut microbiome and cancer. Gut dysbiosis is an imbalance commensal pathogenic bacteria production microbial antigens metabolites. The immune system interact to maintain homeostasis gut, alterations in composition lead dysregulation, promoting chronic inflammation development tumors. microorganisms their toxic metabolites may migrate other parts body via circulatory system, causing physiological status host secretion various neuroactive molecules through gut-brain axis, gut-hepatic gut-lung axis affect tumorigenesis specific organs. Thus, microbiota can be used as a tumor marker provide new insights into pathogenesis malignant

Language: Английский

Citations

115