Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma
Ku70, a DNA repair protein, binds to the damaged DNA ends and orchestrates the recruitment of other proteins to facilitate repair of DNA double-strand breaks. Besides its essential role in DNA repair, several studies have highlighted nonclassical functions of Ku70 in cellular processes. However, its...
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| Veröffentlicht in: | The Journal of clinical investigation 2024-12, Vol.134 (23), p.1-17 |
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| creator | Huang, Qianru Tian, Na Zhang, Jianfeng Song, Shiyang Cheng, Hao Liu, Xinnan Zhang, Wenle Ye, Youqiong Du, Yanhua Dai, Xueyu Liang, Rui Li, Dan Dai, Sheng-Ming Wang, Chuan Chen, Zhi Zhou, Qianjun Li, Bin |
| description | Ku70, a DNA repair protein, binds to the damaged DNA ends and orchestrates the recruitment of other proteins to facilitate repair of DNA double-strand breaks. Besides its essential role in DNA repair, several studies have highlighted nonclassical functions of Ku70 in cellular processes. However, its function in immune homeostasis and antitumor immunity remains unknown. Here, we discovered a marked association between elevated Ku70 expression and unfavorable prognosis in lung adenocarcinoma, focusing specifically on increased Ku70 levels in tumor-infiltrated Tregs. Using a lung-colonizing tumor model in mice with Treg-specific Ku70 deficiency, we demonstrated that deletion of Ku70 in Tregs led to a stronger antitumor response and slower tumor growth due to impaired immune-suppressive capacity of Tregs. Furthermore, we confirmed that Ku70 played a critical role in sustaining the suppressive function of human Tregs. We found that Ku70 bound to forkhead box protein P3 (FOXP3) and occupied FOXP3-bound genomic sites to support its transcriptional activities. These findings not only unveil a nonhomologous end joining-independent (NHEJ-independent) role of Ku70 crucial for Treg-suppressive function, but also underscore the potential of targeting Ku70 as an effective strategy in cancer therapy, aiming to both restrain cancer cells and enhance pulmonary antitumor immunity. |
| doi_str_mv | 10.1172/JCI178079 |
| format | Article |
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Besides its essential role in DNA repair, several studies have highlighted nonclassical functions of Ku70 in cellular processes. However, its function in immune homeostasis and antitumor immunity remains unknown. Here, we discovered a marked association between elevated Ku70 expression and unfavorable prognosis in lung adenocarcinoma, focusing specifically on increased Ku70 levels in tumor-infiltrated Tregs. Using a lung-colonizing tumor model in mice with Treg-specific Ku70 deficiency, we demonstrated that deletion of Ku70 in Tregs led to a stronger antitumor response and slower tumor growth due to impaired immune-suppressive capacity of Tregs. Furthermore, we confirmed that Ku70 played a critical role in sustaining the suppressive function of human Tregs. We found that Ku70 bound to forkhead box protein P3 (FOXP3) and occupied FOXP3-bound genomic sites to support its transcriptional activities. These findings not only unveil a nonhomologous end joining-independent (NHEJ-independent) role of Ku70 crucial for Treg-suppressive function, but also underscore the potential of targeting Ku70 as an effective strategy in cancer therapy, aiming to both restrain cancer cells and enhance pulmonary antitumor immunity.</description><identifier>ISSN: 1558-8238</identifier><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI178079</identifier><identifier>PMID: 39446493</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - immunology ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Adenocarcinoma of Lung - genetics ; Adenocarcinoma of Lung - immunology ; Adenocarcinoma of Lung - metabolism ; Adenocarcinoma of Lung - pathology ; Animals ; Antitumor activity ; Cancer therapies ; Cell Line, Tumor ; Chemotherapy ; Cytokines ; Cytotoxicity ; DNA damage ; DNA End-Joining Repair ; DNA repair ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - immunology ; DNA-Binding Proteins - metabolism ; Female ; Forkhead protein ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - immunology ; Forkhead Transcription Factors - metabolism ; Foxp3 protein ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Health aspects ; Homeostasis ; Humans ; Immunity ; Ku Autoantigen - genetics ; Ku Autoantigen - immunology ; Ku Autoantigen - metabolism ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - immunology ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Lymphocytes ; Lymphocytes T ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Non-homologous end joining ; Physiological aspects ; Proteins ; Radiation therapy ; Spleen ; T cell receptors ; T cells ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - pathology ; Thymus gland ; Tumors</subject><ispartof>The Journal of clinical investigation, 2024-12, Vol.134 (23), p.1-17</ispartof><rights>COPYRIGHT 2024 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Dec 2024</rights><rights>2024 Huang et al. 2024 Huang et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3788-42f51c8bf388af1742d9ce25de8ad0d8af2db49581a589ec550cef31e738519c3</cites><orcidid>0000-0001-8332-4710 ; 0000-0002-7640-8884</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/PMC11601948/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601948/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39446493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Qianru</creatorcontrib><creatorcontrib>Tian, Na</creatorcontrib><creatorcontrib>Zhang, Jianfeng</creatorcontrib><creatorcontrib>Song, Shiyang</creatorcontrib><creatorcontrib>Cheng, Hao</creatorcontrib><creatorcontrib>Liu, Xinnan</creatorcontrib><creatorcontrib>Zhang, Wenle</creatorcontrib><creatorcontrib>Ye, Youqiong</creatorcontrib><creatorcontrib>Du, Yanhua</creatorcontrib><creatorcontrib>Dai, Xueyu</creatorcontrib><creatorcontrib>Liang, Rui</creatorcontrib><creatorcontrib>Li, Dan</creatorcontrib><creatorcontrib>Dai, Sheng-Ming</creatorcontrib><creatorcontrib>Wang, Chuan</creatorcontrib><creatorcontrib>Chen, Zhi</creatorcontrib><creatorcontrib>Zhou, Qianjun</creatorcontrib><creatorcontrib>Li, Bin</creatorcontrib><title>Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Ku70, a DNA repair protein, binds to the damaged DNA ends and orchestrates the recruitment of other proteins to facilitate repair of DNA double-strand breaks. Besides its essential role in DNA repair, several studies have highlighted nonclassical functions of Ku70 in cellular processes. However, its function in immune homeostasis and antitumor immunity remains unknown. Here, we discovered a marked association between elevated Ku70 expression and unfavorable prognosis in lung adenocarcinoma, focusing specifically on increased Ku70 levels in tumor-infiltrated Tregs. Using a lung-colonizing tumor model in mice with Treg-specific Ku70 deficiency, we demonstrated that deletion of Ku70 in Tregs led to a stronger antitumor response and slower tumor growth due to impaired immune-suppressive capacity of Tregs. Furthermore, we confirmed that Ku70 played a critical role in sustaining the suppressive function of human Tregs. We found that Ku70 bound to forkhead box protein P3 (FOXP3) and occupied FOXP3-bound genomic sites to support its transcriptional activities. These findings not only unveil a nonhomologous end joining-independent (NHEJ-independent) role of Ku70 crucial for Treg-suppressive function, but also underscore the potential of targeting Ku70 as an effective strategy in cancer therapy, aiming to both restrain cancer cells and enhance pulmonary antitumor immunity.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - immunology</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma of Lung - genetics</subject><subject>Adenocarcinoma of Lung - immunology</subject><subject>Adenocarcinoma of Lung - metabolism</subject><subject>Adenocarcinoma of Lung - pathology</subject><subject>Animals</subject><subject>Antitumor activity</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>DNA damage</subject><subject>DNA End-Joining Repair</subject><subject>DNA repair</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - immunology</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Female</subject><subject>Forkhead protein</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - immunology</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Foxp3 protein</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Immunity</subject><subject>Ku Autoantigen - genetics</subject><subject>Ku Autoantigen - immunology</subject><subject>Ku Autoantigen - metabolism</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - immunology</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Non-homologous end joining</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Radiation therapy</subject><subject>Spleen</subject><subject>T cell receptors</subject><subject>T cells</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - pathology</subject><subject>Thymus gland</subject><subject>Tumors</subject><issn>1558-8238</issn><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqN0kFv0zAUB_AIgdgYHPgCyBISgkOGHduNfUJTxaAwUQQDcbNc5yX1lNjBjif27XG1UVrUA8oh0cvPfz_LryieEnxKSF29_jBfkFrgWt4rjgnnohQVFfd3vo-KRzFeYUwY4-xhcUQlYzMm6XFx88k70-sYrdE90may3iHfoo-pxmgMfvATRHQZoCtjGscAWV4DapO7pdM6-NStkUbnyx-fadnACK4BN6EBzFo7GwdkHeqT65DOdW90MNb5QT8uHrS6j_Dk7n1SfDt_ezl_X14s3y3mZxelobUQJataToxYtVQI3ZKaVY00UPEGhG5wk2tVs2KSC6K5kGA4xwZaSqCmghNp6Enx5jZ3TKsBGpN7C7pXY7CDDjfKa6v2_zi7Vp2_VoTMMJFM5ISXdwnB_0wQJzXYaKDvtQOfoqKkwlxSWdWZPv-HXvkUXD5fVoxlM6Pkr-p0D8q61ueNzSZUnYmcJSTBMqvygOrAQe7SO2htLu_50wM-Pw0M1hxc8GpvQTYT_Jo6nWJUi69f_t8uv-_bFzt2Dbqf1tH3aTMw8WCoCT7GAO32VghWm8lW28nO9tnuNW7ln1GmvwFy2_Bl</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Huang, Qianru</creator><creator>Tian, Na</creator><creator>Zhang, Jianfeng</creator><creator>Song, Shiyang</creator><creator>Cheng, Hao</creator><creator>Liu, Xinnan</creator><creator>Zhang, Wenle</creator><creator>Ye, Youqiong</creator><creator>Du, Yanhua</creator><creator>Dai, Xueyu</creator><creator>Liang, Rui</creator><creator>Li, Dan</creator><creator>Dai, Sheng-Ming</creator><creator>Wang, Chuan</creator><creator>Chen, Zhi</creator><creator>Zhou, Qianjun</creator><creator>Li, Bin</creator><general>American Society for Clinical Investigation</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8332-4710</orcidid><orcidid>https://orcid.org/0000-0002-7640-8884</orcidid></search><sort><creationdate>20241201</creationdate><title>Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma</title><author>Huang, Qianru ; Tian, Na ; Zhang, Jianfeng ; Song, Shiyang ; Cheng, Hao ; Liu, Xinnan ; Zhang, Wenle ; Ye, Youqiong ; Du, Yanhua ; Dai, Xueyu ; Liang, Rui ; Li, Dan ; Dai, Sheng-Ming ; Wang, Chuan ; Chen, Zhi ; Zhou, Qianjun ; Li, Bin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3788-42f51c8bf388af1742d9ce25de8ad0d8af2db49581a589ec550cef31e738519c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - immunology</topic><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma of Lung - genetics</topic><topic>Adenocarcinoma of Lung - immunology</topic><topic>Adenocarcinoma of Lung - metabolism</topic><topic>Adenocarcinoma of Lung - pathology</topic><topic>Animals</topic><topic>Antitumor activity</topic><topic>Cancer therapies</topic><topic>Cell Line, Tumor</topic><topic>Chemotherapy</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>DNA damage</topic><topic>DNA End-Joining Repair</topic><topic>DNA repair</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - immunology</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Female</topic><topic>Forkhead protein</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - immunology</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Foxp3 protein</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Immunity</topic><topic>Ku Autoantigen - genetics</topic><topic>Ku Autoantigen - immunology</topic><topic>Ku Autoantigen - metabolism</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - immunology</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Non-homologous end joining</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Radiation therapy</topic><topic>Spleen</topic><topic>T cell receptors</topic><topic>T cells</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - pathology</topic><topic>Thymus gland</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Qianru</creatorcontrib><creatorcontrib>Tian, Na</creatorcontrib><creatorcontrib>Zhang, Jianfeng</creatorcontrib><creatorcontrib>Song, Shiyang</creatorcontrib><creatorcontrib>Cheng, Hao</creatorcontrib><creatorcontrib>Liu, Xinnan</creatorcontrib><creatorcontrib>Zhang, Wenle</creatorcontrib><creatorcontrib>Ye, Youqiong</creatorcontrib><creatorcontrib>Du, Yanhua</creatorcontrib><creatorcontrib>Dai, Xueyu</creatorcontrib><creatorcontrib>Liang, Rui</creatorcontrib><creatorcontrib>Li, Dan</creatorcontrib><creatorcontrib>Dai, Sheng-Ming</creatorcontrib><creatorcontrib>Wang, Chuan</creatorcontrib><creatorcontrib>Chen, Zhi</creatorcontrib><creatorcontrib>Zhou, Qianjun</creatorcontrib><creatorcontrib>Li, Bin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</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>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</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 Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Qianru</au><au>Tian, Na</au><au>Zhang, Jianfeng</au><au>Song, Shiyang</au><au>Cheng, Hao</au><au>Liu, Xinnan</au><au>Zhang, Wenle</au><au>Ye, Youqiong</au><au>Du, Yanhua</au><au>Dai, Xueyu</au><au>Liang, Rui</au><au>Li, Dan</au><au>Dai, Sheng-Ming</au><au>Wang, Chuan</au><au>Chen, Zhi</au><au>Zhou, Qianjun</au><au>Li, Bin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>134</volume><issue>23</issue><spage>1</spage><epage>17</epage><pages>1-17</pages><issn>1558-8238</issn><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>Ku70, a DNA repair protein, binds to the damaged DNA ends and orchestrates the recruitment of other proteins to facilitate repair of DNA double-strand breaks. Besides its essential role in DNA repair, several studies have highlighted nonclassical functions of Ku70 in cellular processes. However, its function in immune homeostasis and antitumor immunity remains unknown. Here, we discovered a marked association between elevated Ku70 expression and unfavorable prognosis in lung adenocarcinoma, focusing specifically on increased Ku70 levels in tumor-infiltrated Tregs. Using a lung-colonizing tumor model in mice with Treg-specific Ku70 deficiency, we demonstrated that deletion of Ku70 in Tregs led to a stronger antitumor response and slower tumor growth due to impaired immune-suppressive capacity of Tregs. Furthermore, we confirmed that Ku70 played a critical role in sustaining the suppressive function of human Tregs. We found that Ku70 bound to forkhead box protein P3 (FOXP3) and occupied FOXP3-bound genomic sites to support its transcriptional activities. These findings not only unveil a nonhomologous end joining-independent (NHEJ-independent) role of Ku70 crucial for Treg-suppressive function, but also underscore the potential of targeting Ku70 as an effective strategy in cancer therapy, aiming to both restrain cancer cells and enhance pulmonary antitumor immunity.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>39446493</pmid><doi>10.1172/JCI178079</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-8332-4710</orcidid><orcidid>https://orcid.org/0000-0002-7640-8884</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of clinical investigation, 2024-12, Vol.134 (23), p.1-17 |
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| language | eng |
| recordid | cdi_crossref_primary_10_1172_JCI178079 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - immunology Adenocarcinoma - metabolism Adenocarcinoma - pathology Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - immunology Adenocarcinoma of Lung - metabolism Adenocarcinoma of Lung - pathology Animals Antitumor activity Cancer therapies Cell Line, Tumor Chemotherapy Cytokines Cytotoxicity DNA damage DNA End-Joining Repair DNA repair DNA-Binding Proteins - genetics DNA-Binding Proteins - immunology DNA-Binding Proteins - metabolism Female Forkhead protein Forkhead Transcription Factors - genetics Forkhead Transcription Factors - immunology Forkhead Transcription Factors - metabolism Foxp3 protein Gene Expression Regulation, Neoplastic Genetic aspects Health aspects Homeostasis Humans Immunity Ku Autoantigen - genetics Ku Autoantigen - immunology Ku Autoantigen - metabolism Lung cancer Lung Neoplasms - genetics Lung Neoplasms - immunology Lung Neoplasms - metabolism Lung Neoplasms - pathology Lymphocytes Lymphocytes T Mice Mice, Inbred C57BL Mice, Knockout Non-homologous end joining Physiological aspects Proteins Radiation therapy Spleen T cell receptors T cells T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - pathology Thymus gland Tumors |
| title | Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma |
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