Massively recruited sTLR9+ neutrophils in rapidly formed nodules at the site of tumor cell inoculation and their contribution to a pro-tumor microenvironment
Neutrophils exert either pro- or anti-tumor activities. However, few studies have focused on neutrophils at the tumor initiation stage. In this study, we unexpectedly found a subcutaneous nodule in the groin areas of mice inoculated with tumor cells. The nodule was developed 24 h after the inoculati...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2023-08, Vol.72 (8), p.2671-2686 |
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| creator | Kou, Mengyuan Lu, Wenting Zhu, Mengru Qu, Kuo Wang, Liying Yu, Yongli |
| description | Neutrophils exert either pro- or anti-tumor activities. However, few studies have focused on neutrophils at the tumor initiation stage. In this study, we unexpectedly found a subcutaneous nodule in the groin areas of mice inoculated with tumor cells. The nodule was developed 24 h after the inoculation, filled with tumor cells and massively recruited neutrophils, being designated as tumor nodules. 22% of the neutrophils in tumor nodules are surface TLR9 (sTLR9) expressing neutrophils (sTLR9
+
neutrophils). With tumor progression, sTLR9
+
neutrophils were sustainably increased in tumor nodules/tumor tissues, reaching to 90.8% on day 13 after inoculation, with increased expression of IL-10 and decreased or no expression of TNFα. In vivo administration of CpG 5805 significantly reduced sTLR9 expression of the sTLR9
+
neutrophils. The reduction of sTLR9 on neutrophils in tumor nodules contributed to the induction of an anti-tumor microenvironment conductive to the inhibition of tumor growth. Overall, the study provides insights for understanding the role of sTLR9
+
neutrophils in the tumor development, especially in the early stage.
Graphical abstract |
| doi_str_mv | 10.1007/s00262-023-03451-1 |
| format | Article |
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+
neutrophils). With tumor progression, sTLR9
+
neutrophils were sustainably increased in tumor nodules/tumor tissues, reaching to 90.8% on day 13 after inoculation, with increased expression of IL-10 and decreased or no expression of TNFα. In vivo administration of CpG 5805 significantly reduced sTLR9 expression of the sTLR9
+
neutrophils. The reduction of sTLR9 on neutrophils in tumor nodules contributed to the induction of an anti-tumor microenvironment conductive to the inhibition of tumor growth. Overall, the study provides insights for understanding the role of sTLR9
+
neutrophils in the tumor development, especially in the early stage.
Graphical abstract</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-023-03451-1</identifier><identifier>PMID: 37079065</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Antitumor agents ; Cancer Research ; Immunology ; Inoculation ; Interleukin 10 ; Leukocytes (neutrophilic) ; Medicine ; Medicine & Public Health ; Mice ; Neutrophils ; Neutrophils - metabolism ; Nodules ; Oncology ; TLR9 protein ; Toll-Like Receptor 9 - metabolism ; Toll-like receptors ; Tumor cells ; Tumor microenvironment ; Tumors</subject><ispartof>Cancer Immunology, Immunotherapy, 2023-08, Vol.72 (8), p.2671-2686</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-551085757c925cab8b7fcbdbb2ccc6709edd84e9859bbc34e73d96851d97e7853</citedby><cites>FETCH-LOGICAL-c431t-551085757c925cab8b7fcbdbb2ccc6709edd84e9859bbc34e73d96851d97e7853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10992372/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10992372/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37079065$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kou, Mengyuan</creatorcontrib><creatorcontrib>Lu, Wenting</creatorcontrib><creatorcontrib>Zhu, Mengru</creatorcontrib><creatorcontrib>Qu, Kuo</creatorcontrib><creatorcontrib>Wang, Liying</creatorcontrib><creatorcontrib>Yu, Yongli</creatorcontrib><title>Massively recruited sTLR9+ neutrophils in rapidly formed nodules at the site of tumor cell inoculation and their contribution to a pro-tumor microenvironment</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Neutrophils exert either pro- or anti-tumor activities. However, few studies have focused on neutrophils at the tumor initiation stage. In this study, we unexpectedly found a subcutaneous nodule in the groin areas of mice inoculated with tumor cells. The nodule was developed 24 h after the inoculation, filled with tumor cells and massively recruited neutrophils, being designated as tumor nodules. 22% of the neutrophils in tumor nodules are surface TLR9 (sTLR9) expressing neutrophils (sTLR9
+
neutrophils). With tumor progression, sTLR9
+
neutrophils were sustainably increased in tumor nodules/tumor tissues, reaching to 90.8% on day 13 after inoculation, with increased expression of IL-10 and decreased or no expression of TNFα. In vivo administration of CpG 5805 significantly reduced sTLR9 expression of the sTLR9
+
neutrophils. The reduction of sTLR9 on neutrophils in tumor nodules contributed to the induction of an anti-tumor microenvironment conductive to the inhibition of tumor growth. Overall, the study provides insights for understanding the role of sTLR9
+
neutrophils in the tumor development, especially in the early stage.
Graphical abstract</description><subject>Animals</subject><subject>Antitumor agents</subject><subject>Cancer Research</subject><subject>Immunology</subject><subject>Inoculation</subject><subject>Interleukin 10</subject><subject>Leukocytes (neutrophilic)</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Neutrophils</subject><subject>Neutrophils - metabolism</subject><subject>Nodules</subject><subject>Oncology</subject><subject>TLR9 protein</subject><subject>Toll-Like Receptor 9 - metabolism</subject><subject>Toll-like receptors</subject><subject>Tumor cells</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kcuKFDEUhoMoTjv6Ai4k4EYYSnOpVCorkcFRoUWQcR1SqdR0hqqkzaVhHsZ39fTUOF4WrhLO-f6TnP9H6Dklrykh8k0mhHWsIYw3hLeCNvQB2tCWQ6kX9CHaQJU0kpD2BD3J-RoujCj1GJ1wSaQindigH59Nzv7g5hucnE3VFzfifLn9qs5wcLWkuN_5OWMfcDJ7PwI3xbQAFOJYZ5exKbjsHM6gxHHCpS4xYevmGTTR1tkUHwM2YTxiHloxlOSHelsuERu8T7FZZYu3Kbpw8CmGxYXyFD2azJzds7vzFH27eH95_rHZfvnw6fzdtrEtp6URgsLGUkirmLBm6Ac52WEcBmat7SRRbhz71qleqGGwvHWSj6oDj0YlnewFP0Vv17n7OsBuFp5OZtb75BeTbnQ0Xv_dCX6nr-JBU_CTcclgwqu7CSl-ry4Xvfh8dMEEF2vWrCdcdVyxI_ryH_Q61hRgP6Ba0lIhJAeKrRQ4knNy0_1vKNHH-PUav4b49W38moLoxZ973Et-5Q0AX4EMrXDl0u-3_zP2J-JQv1w</recordid><startdate>20230801</startdate><enddate>20230801</enddate><creator>Kou, Mengyuan</creator><creator>Lu, Wenting</creator><creator>Zhu, Mengru</creator><creator>Qu, Kuo</creator><creator>Wang, Liying</creator><creator>Yu, Yongli</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</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>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230801</creationdate><title>Massively recruited sTLR9+ neutrophils in rapidly formed nodules at the site of tumor cell inoculation and their contribution to a pro-tumor microenvironment</title><author>Kou, Mengyuan ; Lu, Wenting ; Zhu, Mengru ; Qu, Kuo ; Wang, Liying ; Yu, Yongli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-551085757c925cab8b7fcbdbb2ccc6709edd84e9859bbc34e73d96851d97e7853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Antitumor agents</topic><topic>Cancer Research</topic><topic>Immunology</topic><topic>Inoculation</topic><topic>Interleukin 10</topic><topic>Leukocytes (neutrophilic)</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Neutrophils</topic><topic>Neutrophils - metabolism</topic><topic>Nodules</topic><topic>Oncology</topic><topic>TLR9 protein</topic><topic>Toll-Like Receptor 9 - metabolism</topic><topic>Toll-like receptors</topic><topic>Tumor cells</topic><topic>Tumor microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kou, Mengyuan</creatorcontrib><creatorcontrib>Lu, Wenting</creatorcontrib><creatorcontrib>Zhu, Mengru</creatorcontrib><creatorcontrib>Qu, Kuo</creatorcontrib><creatorcontrib>Wang, Liying</creatorcontrib><creatorcontrib>Yu, Yongli</creatorcontrib><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>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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>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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kou, Mengyuan</au><au>Lu, Wenting</au><au>Zhu, Mengru</au><au>Qu, Kuo</au><au>Wang, Liying</au><au>Yu, Yongli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Massively recruited sTLR9+ neutrophils in rapidly formed nodules at the site of tumor cell inoculation and their contribution to a pro-tumor microenvironment</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2023-08-01</date><risdate>2023</risdate><volume>72</volume><issue>8</issue><spage>2671</spage><epage>2686</epage><pages>2671-2686</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Neutrophils exert either pro- or anti-tumor activities. However, few studies have focused on neutrophils at the tumor initiation stage. In this study, we unexpectedly found a subcutaneous nodule in the groin areas of mice inoculated with tumor cells. The nodule was developed 24 h after the inoculation, filled with tumor cells and massively recruited neutrophils, being designated as tumor nodules. 22% of the neutrophils in tumor nodules are surface TLR9 (sTLR9) expressing neutrophils (sTLR9
+
neutrophils). With tumor progression, sTLR9
+
neutrophils were sustainably increased in tumor nodules/tumor tissues, reaching to 90.8% on day 13 after inoculation, with increased expression of IL-10 and decreased or no expression of TNFα. In vivo administration of CpG 5805 significantly reduced sTLR9 expression of the sTLR9
+
neutrophils. The reduction of sTLR9 on neutrophils in tumor nodules contributed to the induction of an anti-tumor microenvironment conductive to the inhibition of tumor growth. Overall, the study provides insights for understanding the role of sTLR9
+
neutrophils in the tumor development, especially in the early stage.
Graphical abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>37079065</pmid><doi>10.1007/s00262-023-03451-1</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | Animals Antitumor agents Cancer Research Immunology Inoculation Interleukin 10 Leukocytes (neutrophilic) Medicine Medicine & Public Health Mice Neutrophils Neutrophils - metabolism Nodules Oncology TLR9 protein Toll-Like Receptor 9 - metabolism Toll-like receptors Tumor cells Tumor microenvironment Tumors |
| title | Massively recruited sTLR9+ neutrophils in rapidly formed nodules at the site of tumor cell inoculation and their contribution to a pro-tumor microenvironment |
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