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B cell lymphoma 6 promotes hepatocellular carcinoma progression by inhibiting tumor infiltrating CD4+T cell cytotoxicity through ESM1
Immunotherapy exhibited potential effects for advanced hepatocellular carcinoma, unfortunately, the clinical benefits are often countered by cancer adaptive immune suppressive response. Uncovering the mechanism how cancer cells evade immune surveillance would help to develop new immunotherapy approa...
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Published in: | NPJ precision oncology 2024-07, Vol.8 (1), p.139-16, Article 139 |
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creator | Li, Jiatao Feng, Juan Li, Ziyong Ni, Yuanli Liu, Limei Lei, Xia Chai, Zixuan Zhuang, Na Xu, Jiake He, Yongpeng Shan, Juanjuan Qian, Cheng |
description | Immunotherapy exhibited potential effects for advanced hepatocellular carcinoma, unfortunately, the clinical benefits are often countered by cancer adaptive immune suppressive response. Uncovering the mechanism how cancer cells evade immune surveillance would help to develop new immunotherapy approaches and combination therapy. In this article, by analyzing the transcriptional factors which modulate the differentially expressed genes between T cell infiltration high group and low group, we identified oncoprotein B cell lymphoma 6 (BCL6) suppresses the infiltration and activation of tumor infiltrating T lymphocytes, thus correlated with poorer clinical outcome. By using antibody deletion experiment, we further demonstrated that CD4
+
T cells but not CD8
+
T cells are the main lymphocyte population suppressed by Bcl6 to promote HCC development. Mechanistically, BCL6 decreases cancer cell expression of pro-inflammatory cytokines and T lymphocyte chemokines such as IL6, IL1F6, and CCL5. Moreover, BCL6 upregulates Endothelial cell-specific molecule 1 (ESM1) to inhibit T lymphocyte recruitment and activation possibly through ICAM-1/LFA-1 signaling pathway. Our findings uncovered an unappreciated paracrine mechanism how cancer cell-derived BCL6 assists cancer cell immune evasion, and highlighted the role of CD4
+
T cells in HCC immune surveillance. |
doi_str_mv | 10.1038/s41698-024-00625-7 |
format | article |
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+
T cells but not CD8
+
T cells are the main lymphocyte population suppressed by Bcl6 to promote HCC development. Mechanistically, BCL6 decreases cancer cell expression of pro-inflammatory cytokines and T lymphocyte chemokines such as IL6, IL1F6, and CCL5. Moreover, BCL6 upregulates Endothelial cell-specific molecule 1 (ESM1) to inhibit T lymphocyte recruitment and activation possibly through ICAM-1/LFA-1 signaling pathway. Our findings uncovered an unappreciated paracrine mechanism how cancer cell-derived BCL6 assists cancer cell immune evasion, and highlighted the role of CD4
+
T cells in HCC immune surveillance.</description><identifier>ISSN: 2397-768X</identifier><identifier>EISSN: 2397-768X</identifier><identifier>DOI: 10.1038/s41698-024-00625-7</identifier><identifier>PMID: 38956432</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/580/1884 ; 692/4028/67/395 ; Antigens ; Cancer Research ; Cancer therapies ; Cell death ; Clinical outcomes ; Cytokines ; Cytotoxicity ; DNA repair ; Gene Therapy ; Genomes ; Human Genetics ; Immunotherapy ; Internal Medicine ; Leukemia ; Liver cancer ; Lymphocytes ; Lymphoma ; Medicine ; Medicine & Public Health ; Oncology ; Patients ; Proteins ; Transcription factors</subject><ispartof>NPJ precision oncology, 2024-07, Vol.8 (1), p.139-16, Article 139</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c378t-73da74e349aeb32fb777ec235b47af15a96d015f0f75c690d69369f9e46867fe3</cites><orcidid>0000-0002-0640-1652 ; 0009-0006-2546-7602 ; 0000-0003-1500-9991 ; 0000-0002-9277-6855</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220024/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3074884469?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38956432$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Jiatao</creatorcontrib><creatorcontrib>Feng, Juan</creatorcontrib><creatorcontrib>Li, Ziyong</creatorcontrib><creatorcontrib>Ni, Yuanli</creatorcontrib><creatorcontrib>Liu, Limei</creatorcontrib><creatorcontrib>Lei, Xia</creatorcontrib><creatorcontrib>Chai, Zixuan</creatorcontrib><creatorcontrib>Zhuang, Na</creatorcontrib><creatorcontrib>Xu, Jiake</creatorcontrib><creatorcontrib>He, Yongpeng</creatorcontrib><creatorcontrib>Shan, Juanjuan</creatorcontrib><creatorcontrib>Qian, Cheng</creatorcontrib><title>B cell lymphoma 6 promotes hepatocellular carcinoma progression by inhibiting tumor infiltrating CD4+T cell cytotoxicity through ESM1</title><title>NPJ precision oncology</title><addtitle>npj Precis. Onc</addtitle><addtitle>NPJ Precis Oncol</addtitle><description>Immunotherapy exhibited potential effects for advanced hepatocellular carcinoma, unfortunately, the clinical benefits are often countered by cancer adaptive immune suppressive response. Uncovering the mechanism how cancer cells evade immune surveillance would help to develop new immunotherapy approaches and combination therapy. In this article, by analyzing the transcriptional factors which modulate the differentially expressed genes between T cell infiltration high group and low group, we identified oncoprotein B cell lymphoma 6 (BCL6) suppresses the infiltration and activation of tumor infiltrating T lymphocytes, thus correlated with poorer clinical outcome. By using antibody deletion experiment, we further demonstrated that CD4
+
T cells but not CD8
+
T cells are the main lymphocyte population suppressed by Bcl6 to promote HCC development. Mechanistically, BCL6 decreases cancer cell expression of pro-inflammatory cytokines and T lymphocyte chemokines such as IL6, IL1F6, and CCL5. Moreover, BCL6 upregulates Endothelial cell-specific molecule 1 (ESM1) to inhibit T lymphocyte recruitment and activation possibly through ICAM-1/LFA-1 signaling pathway. Our findings uncovered an unappreciated paracrine mechanism how cancer cell-derived BCL6 assists cancer cell immune evasion, and highlighted the role of CD4
+
T cells in HCC immune surveillance.</description><subject>631/67/580/1884</subject><subject>692/4028/67/395</subject><subject>Antigens</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Cell death</subject><subject>Clinical outcomes</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>DNA repair</subject><subject>Gene Therapy</subject><subject>Genomes</subject><subject>Human Genetics</subject><subject>Immunotherapy</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Liver cancer</subject><subject>Lymphocytes</subject><subject>Lymphoma</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Patients</subject><subject>Proteins</subject><subject>Transcription factors</subject><issn>2397-768X</issn><issn>2397-768X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9Us2K1TAYLaI4w3VewIUE3AhSzV-TZiXOddSBEReO4C6kadLm0jbXJBXvA_jeprfjOONCCCR838k5OV9OUTxF8BWCpH4dKWKiLiGmJYQMVyV_UJxiInjJWf3t4Z3zSXEW4w5CiOoKYcYeFyekFhWjBJ8Wv86BNsMAhsO47_2oAAP74EefTAS92avkl_Y8qAC0CtpNCyYjumBidH4CzQG4qXeNS27qQJpHH3LBuiEFdSxt39GX16uIPiSf_E-nXTqA1Ac_dz24-PIJPSkeWTVEc3azb4qv7y-utx_Lq88fLrdvr0pNeJ1KTlrFqSFUKNMQbBvOudGYVA3lyqJKCdZCVFloeaWZgC0ThAkrDGU149aQTXG58rZe7eQ-uFGFg_TKyWPBh06qkJwejNSCU4h52wpSU8GVsMRQi1vNLK50xTPXm5VrPzejabWZsuPhHun9zuR62fkfEiGMYf63zPDihiH477OJSY4uLoNSk_FzlATyinC2rE3x_B_ozs9hyrNaULSuKc1eNwVeUTr4GIOxt69BUC6pkWtqZFaXx9TIxcezuz5ur_zJSAaQFRBza-pM-Kv9H9rf-V_PYg</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>Li, Jiatao</creator><creator>Feng, Juan</creator><creator>Li, Ziyong</creator><creator>Ni, Yuanli</creator><creator>Liu, Limei</creator><creator>Lei, Xia</creator><creator>Chai, Zixuan</creator><creator>Zhuang, Na</creator><creator>Xu, Jiake</creator><creator>He, Yongpeng</creator><creator>Shan, Juanjuan</creator><creator>Qian, Cheng</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</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>KB0</scope><scope>M0S</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0640-1652</orcidid><orcidid>https://orcid.org/0009-0006-2546-7602</orcidid><orcidid>https://orcid.org/0000-0003-1500-9991</orcidid><orcidid>https://orcid.org/0000-0002-9277-6855</orcidid></search><sort><creationdate>20240701</creationdate><title>B cell lymphoma 6 promotes hepatocellular carcinoma progression by inhibiting tumor infiltrating CD4+T cell cytotoxicity through ESM1</title><author>Li, Jiatao ; Feng, Juan ; Li, Ziyong ; Ni, Yuanli ; Liu, Limei ; Lei, Xia ; Chai, Zixuan ; Zhuang, Na ; Xu, Jiake ; He, Yongpeng ; Shan, Juanjuan ; Qian, Cheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-73da74e349aeb32fb777ec235b47af15a96d015f0f75c690d69369f9e46867fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>631/67/580/1884</topic><topic>692/4028/67/395</topic><topic>Antigens</topic><topic>Cancer Research</topic><topic>Cancer therapies</topic><topic>Cell death</topic><topic>Clinical outcomes</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>DNA repair</topic><topic>Gene Therapy</topic><topic>Genomes</topic><topic>Human Genetics</topic><topic>Immunotherapy</topic><topic>Internal Medicine</topic><topic>Leukemia</topic><topic>Liver cancer</topic><topic>Lymphocytes</topic><topic>Lymphoma</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>Patients</topic><topic>Proteins</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Jiatao</creatorcontrib><creatorcontrib>Feng, Juan</creatorcontrib><creatorcontrib>Li, Ziyong</creatorcontrib><creatorcontrib>Ni, Yuanli</creatorcontrib><creatorcontrib>Liu, Limei</creatorcontrib><creatorcontrib>Lei, Xia</creatorcontrib><creatorcontrib>Chai, Zixuan</creatorcontrib><creatorcontrib>Zhuang, Na</creatorcontrib><creatorcontrib>Xu, Jiake</creatorcontrib><creatorcontrib>He, Yongpeng</creatorcontrib><creatorcontrib>Shan, Juanjuan</creatorcontrib><creatorcontrib>Qian, Cheng</creatorcontrib><collection>SpringerOpen</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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)</collection><collection>ProQuest Central</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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Nursing & Allied Health Premium</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><collection>DOAJ Directory of Open Access Journals</collection><jtitle>NPJ precision oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Jiatao</au><au>Feng, Juan</au><au>Li, Ziyong</au><au>Ni, Yuanli</au><au>Liu, Limei</au><au>Lei, Xia</au><au>Chai, Zixuan</au><au>Zhuang, Na</au><au>Xu, Jiake</au><au>He, Yongpeng</au><au>Shan, Juanjuan</au><au>Qian, Cheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>B cell lymphoma 6 promotes hepatocellular carcinoma progression by inhibiting tumor infiltrating CD4+T cell cytotoxicity through ESM1</atitle><jtitle>NPJ precision oncology</jtitle><stitle>npj Precis. Onc</stitle><addtitle>NPJ Precis Oncol</addtitle><date>2024-07-01</date><risdate>2024</risdate><volume>8</volume><issue>1</issue><spage>139</spage><epage>16</epage><pages>139-16</pages><artnum>139</artnum><issn>2397-768X</issn><eissn>2397-768X</eissn><abstract>Immunotherapy exhibited potential effects for advanced hepatocellular carcinoma, unfortunately, the clinical benefits are often countered by cancer adaptive immune suppressive response. Uncovering the mechanism how cancer cells evade immune surveillance would help to develop new immunotherapy approaches and combination therapy. In this article, by analyzing the transcriptional factors which modulate the differentially expressed genes between T cell infiltration high group and low group, we identified oncoprotein B cell lymphoma 6 (BCL6) suppresses the infiltration and activation of tumor infiltrating T lymphocytes, thus correlated with poorer clinical outcome. By using antibody deletion experiment, we further demonstrated that CD4
+
T cells but not CD8
+
T cells are the main lymphocyte population suppressed by Bcl6 to promote HCC development. Mechanistically, BCL6 decreases cancer cell expression of pro-inflammatory cytokines and T lymphocyte chemokines such as IL6, IL1F6, and CCL5. Moreover, BCL6 upregulates Endothelial cell-specific molecule 1 (ESM1) to inhibit T lymphocyte recruitment and activation possibly through ICAM-1/LFA-1 signaling pathway. Our findings uncovered an unappreciated paracrine mechanism how cancer cell-derived BCL6 assists cancer cell immune evasion, and highlighted the role of CD4
+
T cells in HCC immune surveillance.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>38956432</pmid><doi>10.1038/s41698-024-00625-7</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-0640-1652</orcidid><orcidid>https://orcid.org/0009-0006-2546-7602</orcidid><orcidid>https://orcid.org/0000-0003-1500-9991</orcidid><orcidid>https://orcid.org/0000-0002-9277-6855</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 631/67/580/1884 692/4028/67/395 Antigens Cancer Research Cancer therapies Cell death Clinical outcomes Cytokines Cytotoxicity DNA repair Gene Therapy Genomes Human Genetics Immunotherapy Internal Medicine Leukemia Liver cancer Lymphocytes Lymphoma Medicine Medicine & Public Health Oncology Patients Proteins Transcription factors |
title | B cell lymphoma 6 promotes hepatocellular carcinoma progression by inhibiting tumor infiltrating CD4+T cell cytotoxicity through ESM1 |
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