Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers
BackgroundThe gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical...
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| Veröffentlicht in: | Journal for immunotherapy of cancer 2021-12, Vol.9 (12), p.e003334 |
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| creator | Mao, Jinzhu Wang, Dongxu Long, Junyu Yang, Xu Lin, Jianzhen Song, Yiwei Xie, Fucun Xun, Ziyu Wang, Yanyu Wang, Yunchao Li, Yiran Sun, Huishan Xue, Jingnan Song, Yang Zuo, Bangyou Zhang, Junwei Bian, Jin Zhang, Ting Yang, Xiaobo Zhang, Lei Sang, Xinting Zhao, Haitao |
| description | BackgroundThe gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers.MethodsPatients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy.ResultsIn total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance.ConclusionsWe demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enrich |
| doi_str_mv | 10.1136/jitc-2021-003334 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8650503</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2607590438</sourcerecordid><originalsourceid>FETCH-LOGICAL-b461t-73f3141c191584a95f3743f66db28d98361aa5b5ab062e229343d44002e1dc4f3</originalsourceid><addsrcrecordid>eNp1kcFrFTEQh4Motjx79yQBLx5cnUmy2d2LINVWoaAHPYdsNuvLYzfZJlml_715bFur4CmBfPPLzHyEPEd4g8jl24PLpmLAsALgnItH5JRBjRUKJh8_uJ-Qs5QOAIAFa9v2KTnhom04ID8l15drprMzMfQuzJa6RHVKwTid7UB_ubyneW-pmZx3Rk802rQEnyzNgWqfXfX1Q4W016nQbp5XHwoe9XJDnad7u-hcgien4w012hsb0zPyZNRTsme35458v_j47fxTdfXl8vP5-6uqFxJz1fCRo0CDHdat0F098kbwUcqhZ-3QtVyi1nVf6x4ks4x1XPBBCABmcTBi5Dvybstd1n62g7E-Rz2pJbq5dKOCdurvF-_26kf4qVpZQ11WtSOvbgNiuF5tymp2ydhp0t6GNSkmoak7ELwt6Mt_0ENYoy_jbRQgNkcKNqpsO6Vox_tmENRRqToqVUelalNaSl48HOK-4E5gAV5vQD8f_nz637zfzFyrMA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2607501178</pqid></control><display><type>article</type><title>Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers</title><source>BMJ Open Access Journals</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Mao, Jinzhu ; Wang, Dongxu ; Long, Junyu ; Yang, Xu ; Lin, Jianzhen ; Song, Yiwei ; Xie, Fucun ; Xun, Ziyu ; Wang, Yanyu ; Wang, Yunchao ; Li, Yiran ; Sun, Huishan ; Xue, Jingnan ; Song, Yang ; Zuo, Bangyou ; Zhang, Junwei ; Bian, Jin ; Zhang, Ting ; Yang, Xiaobo ; Zhang, Lei ; Sang, Xinting ; Zhao, Haitao</creator><creatorcontrib>Mao, Jinzhu ; Wang, Dongxu ; Long, Junyu ; Yang, Xu ; Lin, Jianzhen ; Song, Yiwei ; Xie, Fucun ; Xun, Ziyu ; Wang, Yanyu ; Wang, Yunchao ; Li, Yiran ; Sun, Huishan ; Xue, Jingnan ; Song, Yang ; Zuo, Bangyou ; Zhang, Junwei ; Bian, Jin ; Zhang, Ting ; Yang, Xiaobo ; Zhang, Lei ; Sang, Xinting ; Zhao, Haitao</creatorcontrib><description>BackgroundThe gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers.MethodsPatients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy.ResultsIn total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance.ConclusionsWe demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enriched in responders are effective biomarkers to predict the clinical response and survival benefit of immunotherapy, which might provide a new therapeutic target to modulate the response to cancer immunotherapy.</description><identifier>ISSN: 2051-1426</identifier><identifier>EISSN: 2051-1426</identifier><identifier>DOI: 10.1136/jitc-2021-003334</identifier><identifier>PMID: 34873013</identifier><language>eng</language><publisher>England: BMJ Publishing Group Ltd</publisher><subject>Apoptosis ; Bile ; Biliary Tract Neoplasms - drug therapy ; Biliary Tract Neoplasms - immunology ; Biliary Tract Neoplasms - microbiology ; Biliary Tract Neoplasms - pathology ; Biomarkers ; Cancer ; Cancer therapies ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - immunology ; Carcinoma, Hepatocellular - microbiology ; Carcinoma, Hepatocellular - pathology ; Chemotherapy ; Cholangiocarcinoma ; Digestive system ; Discriminant analysis ; DNA, Bacterial - analysis ; DNA, Bacterial - genetics ; Feces ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors - therapeutic use ; Immunotherapy ; Immunotherapy Biomarkers ; Liver cancer ; liver neoplasms ; Liver Neoplasms - drug therapy ; Liver Neoplasms - immunology ; Liver Neoplasms - microbiology ; Liver Neoplasms - pathology ; Lymphocytes ; Male ; Melanoma ; Metabolism ; Metabolites ; Metagenomics ; Microbiota ; Middle Aged ; Patients ; Phylogenetics ; Prognosis ; Programmed Cell Death 1 Receptor - antagonists & inhibitors ; Survival analysis ; Survival Rate ; Taxonomy ; tumor biomarkers ; Tumors</subject><ispartof>Journal for immunotherapy of cancer, 2021-12, Vol.9 (12), p.e003334</ispartof><rights>Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2021 Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b461t-73f3141c191584a95f3743f66db28d98361aa5b5ab062e229343d44002e1dc4f3</citedby><cites>FETCH-LOGICAL-b461t-73f3141c191584a95f3743f66db28d98361aa5b5ab062e229343d44002e1dc4f3</cites><orcidid>0000-0002-3444-8044</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jitc.bmj.com/content/9/12/e003334.full.pdf$$EPDF$$P50$$Gbmj$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://jitc.bmj.com/content/9/12/e003334.full$$EHTML$$P50$$Gbmj$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768,55325,77403,77429</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34873013$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mao, Jinzhu</creatorcontrib><creatorcontrib>Wang, Dongxu</creatorcontrib><creatorcontrib>Long, Junyu</creatorcontrib><creatorcontrib>Yang, Xu</creatorcontrib><creatorcontrib>Lin, Jianzhen</creatorcontrib><creatorcontrib>Song, Yiwei</creatorcontrib><creatorcontrib>Xie, Fucun</creatorcontrib><creatorcontrib>Xun, Ziyu</creatorcontrib><creatorcontrib>Wang, Yanyu</creatorcontrib><creatorcontrib>Wang, Yunchao</creatorcontrib><creatorcontrib>Li, Yiran</creatorcontrib><creatorcontrib>Sun, Huishan</creatorcontrib><creatorcontrib>Xue, Jingnan</creatorcontrib><creatorcontrib>Song, Yang</creatorcontrib><creatorcontrib>Zuo, Bangyou</creatorcontrib><creatorcontrib>Zhang, Junwei</creatorcontrib><creatorcontrib>Bian, Jin</creatorcontrib><creatorcontrib>Zhang, Ting</creatorcontrib><creatorcontrib>Yang, Xiaobo</creatorcontrib><creatorcontrib>Zhang, Lei</creatorcontrib><creatorcontrib>Sang, Xinting</creatorcontrib><creatorcontrib>Zhao, Haitao</creatorcontrib><title>Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers</title><title>Journal for immunotherapy of cancer</title><addtitle>J Immunother Cancer</addtitle><addtitle>J Immunother Cancer</addtitle><description>BackgroundThe gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers.MethodsPatients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy.ResultsIn total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance.ConclusionsWe demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enriched in responders are effective biomarkers to predict the clinical response and survival benefit of immunotherapy, which might provide a new therapeutic target to modulate the response to cancer immunotherapy.</description><subject>Apoptosis</subject><subject>Bile</subject><subject>Biliary Tract Neoplasms - drug therapy</subject><subject>Biliary Tract Neoplasms - immunology</subject><subject>Biliary Tract Neoplasms - microbiology</subject><subject>Biliary Tract Neoplasms - pathology</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - immunology</subject><subject>Carcinoma, Hepatocellular - microbiology</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Chemotherapy</subject><subject>Cholangiocarcinoma</subject><subject>Digestive system</subject><subject>Discriminant analysis</subject><subject>DNA, Bacterial - analysis</subject><subject>DNA, Bacterial - genetics</subject><subject>Feces</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gastrointestinal Microbiome</subject><subject>Humans</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Immunotherapy</subject><subject>Immunotherapy Biomarkers</subject><subject>Liver cancer</subject><subject>liver neoplasms</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - immunology</subject><subject>Liver Neoplasms - microbiology</subject><subject>Liver Neoplasms - pathology</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Melanoma</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metagenomics</subject><subject>Microbiota</subject><subject>Middle Aged</subject><subject>Patients</subject><subject>Phylogenetics</subject><subject>Prognosis</subject><subject>Programmed Cell Death 1 Receptor - antagonists & inhibitors</subject><subject>Survival analysis</subject><subject>Survival Rate</subject><subject>Taxonomy</subject><subject>tumor biomarkers</subject><subject>Tumors</subject><issn>2051-1426</issn><issn>2051-1426</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>ACMMV</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcFrFTEQh4Motjx79yQBLx5cnUmy2d2LINVWoaAHPYdsNuvLYzfZJlml_715bFur4CmBfPPLzHyEPEd4g8jl24PLpmLAsALgnItH5JRBjRUKJh8_uJ-Qs5QOAIAFa9v2KTnhom04ID8l15drprMzMfQuzJa6RHVKwTid7UB_ubyneW-pmZx3Rk802rQEnyzNgWqfXfX1Q4W016nQbp5XHwoe9XJDnad7u-hcgien4w012hsb0zPyZNRTsme35458v_j47fxTdfXl8vP5-6uqFxJz1fCRo0CDHdat0F098kbwUcqhZ-3QtVyi1nVf6x4ks4x1XPBBCABmcTBi5Dvybstd1n62g7E-Rz2pJbq5dKOCdurvF-_26kf4qVpZQ11WtSOvbgNiuF5tymp2ydhp0t6GNSkmoak7ELwt6Mt_0ENYoy_jbRQgNkcKNqpsO6Vox_tmENRRqToqVUelalNaSl48HOK-4E5gAV5vQD8f_nz637zfzFyrMA</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Mao, Jinzhu</creator><creator>Wang, Dongxu</creator><creator>Long, Junyu</creator><creator>Yang, Xu</creator><creator>Lin, Jianzhen</creator><creator>Song, Yiwei</creator><creator>Xie, Fucun</creator><creator>Xun, Ziyu</creator><creator>Wang, Yanyu</creator><creator>Wang, Yunchao</creator><creator>Li, Yiran</creator><creator>Sun, Huishan</creator><creator>Xue, Jingnan</creator><creator>Song, Yang</creator><creator>Zuo, Bangyou</creator><creator>Zhang, Junwei</creator><creator>Bian, Jin</creator><creator>Zhang, Ting</creator><creator>Yang, Xiaobo</creator><creator>Zhang, Lei</creator><creator>Sang, Xinting</creator><creator>Zhao, Haitao</creator><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3444-8044</orcidid></search><sort><creationdate>20211201</creationdate><title>Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers</title><author>Mao, Jinzhu ; Wang, Dongxu ; Long, Junyu ; Yang, Xu ; Lin, Jianzhen ; Song, Yiwei ; Xie, Fucun ; Xun, Ziyu ; Wang, Yanyu ; Wang, Yunchao ; Li, Yiran ; Sun, Huishan ; Xue, Jingnan ; Song, Yang ; Zuo, Bangyou ; Zhang, Junwei ; Bian, Jin ; Zhang, Ting ; Yang, Xiaobo ; Zhang, Lei ; Sang, Xinting ; Zhao, Haitao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b461t-73f3141c191584a95f3743f66db28d98361aa5b5ab062e229343d44002e1dc4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Apoptosis</topic><topic>Bile</topic><topic>Biliary Tract Neoplasms - drug therapy</topic><topic>Biliary Tract Neoplasms - immunology</topic><topic>Biliary Tract Neoplasms - microbiology</topic><topic>Biliary Tract Neoplasms - pathology</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - immunology</topic><topic>Carcinoma, Hepatocellular - microbiology</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Chemotherapy</topic><topic>Cholangiocarcinoma</topic><topic>Digestive system</topic><topic>Discriminant analysis</topic><topic>DNA, Bacterial - analysis</topic><topic>DNA, Bacterial - genetics</topic><topic>Feces</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gastrointestinal Microbiome</topic><topic>Humans</topic><topic>Immune Checkpoint Inhibitors - therapeutic use</topic><topic>Immunotherapy</topic><topic>Immunotherapy Biomarkers</topic><topic>Liver cancer</topic><topic>liver neoplasms</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - immunology</topic><topic>Liver Neoplasms - microbiology</topic><topic>Liver Neoplasms - pathology</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Melanoma</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metagenomics</topic><topic>Microbiota</topic><topic>Middle Aged</topic><topic>Patients</topic><topic>Phylogenetics</topic><topic>Prognosis</topic><topic>Programmed Cell Death 1 Receptor - antagonists & inhibitors</topic><topic>Survival analysis</topic><topic>Survival Rate</topic><topic>Taxonomy</topic><topic>tumor biomarkers</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mao, Jinzhu</creatorcontrib><creatorcontrib>Wang, Dongxu</creatorcontrib><creatorcontrib>Long, Junyu</creatorcontrib><creatorcontrib>Yang, Xu</creatorcontrib><creatorcontrib>Lin, Jianzhen</creatorcontrib><creatorcontrib>Song, Yiwei</creatorcontrib><creatorcontrib>Xie, Fucun</creatorcontrib><creatorcontrib>Xun, Ziyu</creatorcontrib><creatorcontrib>Wang, Yanyu</creatorcontrib><creatorcontrib>Wang, Yunchao</creatorcontrib><creatorcontrib>Li, Yiran</creatorcontrib><creatorcontrib>Sun, Huishan</creatorcontrib><creatorcontrib>Xue, Jingnan</creatorcontrib><creatorcontrib>Song, Yang</creatorcontrib><creatorcontrib>Zuo, Bangyou</creatorcontrib><creatorcontrib>Zhang, Junwei</creatorcontrib><creatorcontrib>Bian, Jin</creatorcontrib><creatorcontrib>Zhang, Ting</creatorcontrib><creatorcontrib>Yang, Xiaobo</creatorcontrib><creatorcontrib>Zhang, Lei</creatorcontrib><creatorcontrib>Sang, Xinting</creatorcontrib><creatorcontrib>Zhao, Haitao</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal for immunotherapy of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mao, Jinzhu</au><au>Wang, Dongxu</au><au>Long, Junyu</au><au>Yang, Xu</au><au>Lin, Jianzhen</au><au>Song, Yiwei</au><au>Xie, Fucun</au><au>Xun, Ziyu</au><au>Wang, Yanyu</au><au>Wang, Yunchao</au><au>Li, Yiran</au><au>Sun, Huishan</au><au>Xue, Jingnan</au><au>Song, Yang</au><au>Zuo, Bangyou</au><au>Zhang, Junwei</au><au>Bian, Jin</au><au>Zhang, Ting</au><au>Yang, Xiaobo</au><au>Zhang, Lei</au><au>Sang, Xinting</au><au>Zhao, Haitao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers</atitle><jtitle>Journal for immunotherapy of cancer</jtitle><stitle>J Immunother Cancer</stitle><addtitle>J Immunother Cancer</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>9</volume><issue>12</issue><spage>e003334</spage><pages>e003334-</pages><issn>2051-1426</issn><eissn>2051-1426</eissn><abstract>BackgroundThe gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers.MethodsPatients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy.ResultsIn total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance.ConclusionsWe demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enriched in responders are effective biomarkers to predict the clinical response and survival benefit of immunotherapy, which might provide a new therapeutic target to modulate the response to cancer immunotherapy.</abstract><cop>England</cop><pub>BMJ Publishing Group Ltd</pub><pmid>34873013</pmid><doi>10.1136/jitc-2021-003334</doi><orcidid>https://orcid.org/0000-0002-3444-8044</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2051-1426 |
| ispartof | Journal for immunotherapy of cancer, 2021-12, Vol.9 (12), p.e003334 |
| issn | 2051-1426 2051-1426 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8650503 |
| source | BMJ Open Access Journals; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Apoptosis Bile Biliary Tract Neoplasms - drug therapy Biliary Tract Neoplasms - immunology Biliary Tract Neoplasms - microbiology Biliary Tract Neoplasms - pathology Biomarkers Cancer Cancer therapies Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - immunology Carcinoma, Hepatocellular - microbiology Carcinoma, Hepatocellular - pathology Chemotherapy Cholangiocarcinoma Digestive system Discriminant analysis DNA, Bacterial - analysis DNA, Bacterial - genetics Feces Female Follow-Up Studies Gastrointestinal Microbiome Humans Immune Checkpoint Inhibitors - therapeutic use Immunotherapy Immunotherapy Biomarkers Liver cancer liver neoplasms Liver Neoplasms - drug therapy Liver Neoplasms - immunology Liver Neoplasms - microbiology Liver Neoplasms - pathology Lymphocytes Male Melanoma Metabolism Metabolites Metagenomics Microbiota Middle Aged Patients Phylogenetics Prognosis Programmed Cell Death 1 Receptor - antagonists & inhibitors Survival analysis Survival Rate Taxonomy tumor biomarkers Tumors |
| title | Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers |
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