Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment
The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments...
Gespeichert in:
| Veröffentlicht in: | Cancers 2022-04, Vol.14 (9), p.2152 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 9 |
| container_start_page | 2152 |
| container_title | Cancers |
| container_volume | 14 |
| creator | Tsunokake, Junichi Fujishima, Fumiyoshi Watanabe, Hirofumi Sato, Ikuro Miura, Koh Sakamoto, Kazuhiro Suzuki, Hiroyoshi Sawai, Takashi Itakura, Yuko Hoshi, Tatsuya Kunimitsu, Atsushi Yamauchi, Takuro Akaishi, Ryujiro Ozawa, Yohei Fukutomi, Toshiaki Okamoto, Hiroshi Sato, Chiaki Taniyama, Yusuke Kamei, Takashi Sasano, Hironobu |
| description | The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment. |
| doi_str_mv | 10.3390/cancers14092152 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9100554</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2664796028</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3362-7b8f2c3287ff6411f252b2ad784e6cbb6ee9f25c394b76b7d1e5adad629a5e143</originalsourceid><addsrcrecordid>eNptUk1v1DAQtRCIVqVnbsgSFw6E-iO2Yw5IaCmwUikcytlynDF1ldiLnRT4lfwlvNtSlRWWJVtv3rw3MxqEnlLyinNNTpyNDnKhLdGMCvYAHTKiWCOlbh_e-x-g41KuSD2cUyXVY3TAhZCCdfQQ_b5YppTxp-BygngdcooTxBmHWLGfMOBzWLaRIbkcIuDzFJt9CNJmtGUqr_E6zpCtm0OKuIf5B0DEO4OCbRzwepqWmrCCcSwvd8iXNFe3YEd86j24ueDk9y3fhRrKO9pOuN75EvD_C3-CHnk7Fji-fY_Q1_enF6uPzdnnD-vV27PGcS5Zo_rOM8dZp7yXLaWeCdYzO6iuBen6XgLoijmu217JXg0UhB3sIJm2AmjLj9CbG93N0k8wuGqd7Wg2OUw2_zLJBvNvJIZL8y1dG00JEWIr8OJWIKfvC5TZTKG4OhkbIS3FMClbpSVhXaU-36NepSXH2t6WxTSTrdCVdXLDqgMpJYO_K4YSs90Xs7cvNePZ_R7u-H-3g_8BGtPD9w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2662926459</pqid></control><display><type>article</type><title>Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment</title><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Tsunokake, Junichi ; Fujishima, Fumiyoshi ; Watanabe, Hirofumi ; Sato, Ikuro ; Miura, Koh ; Sakamoto, Kazuhiro ; Suzuki, Hiroyoshi ; Sawai, Takashi ; Itakura, Yuko ; Hoshi, Tatsuya ; Kunimitsu, Atsushi ; Yamauchi, Takuro ; Akaishi, Ryujiro ; Ozawa, Yohei ; Fukutomi, Toshiaki ; Okamoto, Hiroshi ; Sato, Chiaki ; Taniyama, Yusuke ; Kamei, Takashi ; Sasano, Hironobu</creator><creatorcontrib>Tsunokake, Junichi ; Fujishima, Fumiyoshi ; Watanabe, Hirofumi ; Sato, Ikuro ; Miura, Koh ; Sakamoto, Kazuhiro ; Suzuki, Hiroyoshi ; Sawai, Takashi ; Itakura, Yuko ; Hoshi, Tatsuya ; Kunimitsu, Atsushi ; Yamauchi, Takuro ; Akaishi, Ryujiro ; Ozawa, Yohei ; Fukutomi, Toshiaki ; Okamoto, Hiroshi ; Sato, Chiaki ; Taniyama, Yusuke ; Kamei, Takashi ; Sasano, Hironobu</creatorcontrib><description>The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14092152</identifier><identifier>PMID: 35565281</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Algorithms ; Cancer ; Carcinoma ; CD163 antigen ; CD8 antigen ; Cell differentiation ; Chemotherapy ; Foxp3 protein ; Growth factors ; Hospitals ; Immunoreactivity ; Lymphocytes ; Macrophages ; Neoplasia ; Neuroendocrine system ; Neuroendocrine tumors ; Patients ; PD-1 protein ; Tumor cells ; Tumor microenvironment ; Tumor-infiltrating lymphocytes ; Tumors</subject><ispartof>Cancers, 2022-04, Vol.14 (9), p.2152</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3362-7b8f2c3287ff6411f252b2ad784e6cbb6ee9f25c394b76b7d1e5adad629a5e143</citedby><cites>FETCH-LOGICAL-c3362-7b8f2c3287ff6411f252b2ad784e6cbb6ee9f25c394b76b7d1e5adad629a5e143</cites><orcidid>0000-0001-8400-5551 ; 0000-0002-2683-9109 ; 0000-0002-9042-7096 ; 0000-0003-0483-9068 ; 0000-0003-1449-2053 ; 0000-0002-0253-7122</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/PMC9100554/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100554/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35565281$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsunokake, Junichi</creatorcontrib><creatorcontrib>Fujishima, Fumiyoshi</creatorcontrib><creatorcontrib>Watanabe, Hirofumi</creatorcontrib><creatorcontrib>Sato, Ikuro</creatorcontrib><creatorcontrib>Miura, Koh</creatorcontrib><creatorcontrib>Sakamoto, Kazuhiro</creatorcontrib><creatorcontrib>Suzuki, Hiroyoshi</creatorcontrib><creatorcontrib>Sawai, Takashi</creatorcontrib><creatorcontrib>Itakura, Yuko</creatorcontrib><creatorcontrib>Hoshi, Tatsuya</creatorcontrib><creatorcontrib>Kunimitsu, Atsushi</creatorcontrib><creatorcontrib>Yamauchi, Takuro</creatorcontrib><creatorcontrib>Akaishi, Ryujiro</creatorcontrib><creatorcontrib>Ozawa, Yohei</creatorcontrib><creatorcontrib>Fukutomi, Toshiaki</creatorcontrib><creatorcontrib>Okamoto, Hiroshi</creatorcontrib><creatorcontrib>Sato, Chiaki</creatorcontrib><creatorcontrib>Taniyama, Yusuke</creatorcontrib><creatorcontrib>Kamei, Takashi</creatorcontrib><creatorcontrib>Sasano, Hironobu</creatorcontrib><title>Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.</description><subject>Algorithms</subject><subject>Cancer</subject><subject>Carcinoma</subject><subject>CD163 antigen</subject><subject>CD8 antigen</subject><subject>Cell differentiation</subject><subject>Chemotherapy</subject><subject>Foxp3 protein</subject><subject>Growth factors</subject><subject>Hospitals</subject><subject>Immunoreactivity</subject><subject>Lymphocytes</subject><subject>Macrophages</subject><subject>Neoplasia</subject><subject>Neuroendocrine system</subject><subject>Neuroendocrine tumors</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>Tumor cells</subject><subject>Tumor microenvironment</subject><subject>Tumor-infiltrating lymphocytes</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptUk1v1DAQtRCIVqVnbsgSFw6E-iO2Yw5IaCmwUikcytlynDF1ldiLnRT4lfwlvNtSlRWWJVtv3rw3MxqEnlLyinNNTpyNDnKhLdGMCvYAHTKiWCOlbh_e-x-g41KuSD2cUyXVY3TAhZCCdfQQ_b5YppTxp-BygngdcooTxBmHWLGfMOBzWLaRIbkcIuDzFJt9CNJmtGUqr_E6zpCtm0OKuIf5B0DEO4OCbRzwepqWmrCCcSwvd8iXNFe3YEd86j24ueDk9y3fhRrKO9pOuN75EvD_C3-CHnk7Fji-fY_Q1_enF6uPzdnnD-vV27PGcS5Zo_rOM8dZp7yXLaWeCdYzO6iuBen6XgLoijmu217JXg0UhB3sIJm2AmjLj9CbG93N0k8wuGqd7Wg2OUw2_zLJBvNvJIZL8y1dG00JEWIr8OJWIKfvC5TZTKG4OhkbIS3FMClbpSVhXaU-36NepSXH2t6WxTSTrdCVdXLDqgMpJYO_K4YSs90Xs7cvNePZ_R7u-H-3g_8BGtPD9w</recordid><startdate>20220426</startdate><enddate>20220426</enddate><creator>Tsunokake, Junichi</creator><creator>Fujishima, Fumiyoshi</creator><creator>Watanabe, Hirofumi</creator><creator>Sato, Ikuro</creator><creator>Miura, Koh</creator><creator>Sakamoto, Kazuhiro</creator><creator>Suzuki, Hiroyoshi</creator><creator>Sawai, Takashi</creator><creator>Itakura, Yuko</creator><creator>Hoshi, Tatsuya</creator><creator>Kunimitsu, Atsushi</creator><creator>Yamauchi, Takuro</creator><creator>Akaishi, Ryujiro</creator><creator>Ozawa, Yohei</creator><creator>Fukutomi, Toshiaki</creator><creator>Okamoto, Hiroshi</creator><creator>Sato, Chiaki</creator><creator>Taniyama, Yusuke</creator><creator>Kamei, Takashi</creator><creator>Sasano, Hironobu</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</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>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8400-5551</orcidid><orcidid>https://orcid.org/0000-0002-2683-9109</orcidid><orcidid>https://orcid.org/0000-0002-9042-7096</orcidid><orcidid>https://orcid.org/0000-0003-0483-9068</orcidid><orcidid>https://orcid.org/0000-0003-1449-2053</orcidid><orcidid>https://orcid.org/0000-0002-0253-7122</orcidid></search><sort><creationdate>20220426</creationdate><title>Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment</title><author>Tsunokake, Junichi ; Fujishima, Fumiyoshi ; Watanabe, Hirofumi ; Sato, Ikuro ; Miura, Koh ; Sakamoto, Kazuhiro ; Suzuki, Hiroyoshi ; Sawai, Takashi ; Itakura, Yuko ; Hoshi, Tatsuya ; Kunimitsu, Atsushi ; Yamauchi, Takuro ; Akaishi, Ryujiro ; Ozawa, Yohei ; Fukutomi, Toshiaki ; Okamoto, Hiroshi ; Sato, Chiaki ; Taniyama, Yusuke ; Kamei, Takashi ; Sasano, Hironobu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3362-7b8f2c3287ff6411f252b2ad784e6cbb6ee9f25c394b76b7d1e5adad629a5e143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Algorithms</topic><topic>Cancer</topic><topic>Carcinoma</topic><topic>CD163 antigen</topic><topic>CD8 antigen</topic><topic>Cell differentiation</topic><topic>Chemotherapy</topic><topic>Foxp3 protein</topic><topic>Growth factors</topic><topic>Hospitals</topic><topic>Immunoreactivity</topic><topic>Lymphocytes</topic><topic>Macrophages</topic><topic>Neoplasia</topic><topic>Neuroendocrine system</topic><topic>Neuroendocrine tumors</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>Tumor cells</topic><topic>Tumor microenvironment</topic><topic>Tumor-infiltrating lymphocytes</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsunokake, Junichi</creatorcontrib><creatorcontrib>Fujishima, Fumiyoshi</creatorcontrib><creatorcontrib>Watanabe, Hirofumi</creatorcontrib><creatorcontrib>Sato, Ikuro</creatorcontrib><creatorcontrib>Miura, Koh</creatorcontrib><creatorcontrib>Sakamoto, Kazuhiro</creatorcontrib><creatorcontrib>Suzuki, Hiroyoshi</creatorcontrib><creatorcontrib>Sawai, Takashi</creatorcontrib><creatorcontrib>Itakura, Yuko</creatorcontrib><creatorcontrib>Hoshi, Tatsuya</creatorcontrib><creatorcontrib>Kunimitsu, Atsushi</creatorcontrib><creatorcontrib>Yamauchi, Takuro</creatorcontrib><creatorcontrib>Akaishi, Ryujiro</creatorcontrib><creatorcontrib>Ozawa, Yohei</creatorcontrib><creatorcontrib>Fukutomi, Toshiaki</creatorcontrib><creatorcontrib>Okamoto, Hiroshi</creatorcontrib><creatorcontrib>Sato, Chiaki</creatorcontrib><creatorcontrib>Taniyama, Yusuke</creatorcontrib><creatorcontrib>Kamei, Takashi</creatorcontrib><creatorcontrib>Sasano, Hironobu</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</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>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsunokake, Junichi</au><au>Fujishima, Fumiyoshi</au><au>Watanabe, Hirofumi</au><au>Sato, Ikuro</au><au>Miura, Koh</au><au>Sakamoto, Kazuhiro</au><au>Suzuki, Hiroyoshi</au><au>Sawai, Takashi</au><au>Itakura, Yuko</au><au>Hoshi, Tatsuya</au><au>Kunimitsu, Atsushi</au><au>Yamauchi, Takuro</au><au>Akaishi, Ryujiro</au><au>Ozawa, Yohei</au><au>Fukutomi, Toshiaki</au><au>Okamoto, Hiroshi</au><au>Sato, Chiaki</au><au>Taniyama, Yusuke</au><au>Kamei, Takashi</au><au>Sasano, Hironobu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2022-04-26</date><risdate>2022</risdate><volume>14</volume><issue>9</issue><spage>2152</spage><pages>2152-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35565281</pmid><doi>10.3390/cancers14092152</doi><orcidid>https://orcid.org/0000-0001-8400-5551</orcidid><orcidid>https://orcid.org/0000-0002-2683-9109</orcidid><orcidid>https://orcid.org/0000-0002-9042-7096</orcidid><orcidid>https://orcid.org/0000-0003-0483-9068</orcidid><orcidid>https://orcid.org/0000-0003-1449-2053</orcidid><orcidid>https://orcid.org/0000-0002-0253-7122</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2022-04, Vol.14 (9), p.2152 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9100554 |
| source | PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Algorithms Cancer Carcinoma CD163 antigen CD8 antigen Cell differentiation Chemotherapy Foxp3 protein Growth factors Hospitals Immunoreactivity Lymphocytes Macrophages Neoplasia Neuroendocrine system Neuroendocrine tumors Patients PD-1 protein Tumor cells Tumor microenvironment Tumor-infiltrating lymphocytes Tumors |
| title | Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T03%3A43%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Tumor%20Microenvironment%20in%20Mixed%20Neuroendocrine%20Non-Neuroendocrine%20Neoplasms:%20Interaction%20between%20Tumors%20and%20Immune%20Cells,%20and%20Potential%20Effects%20of%20Neuroendocrine%20Differentiation%20on%20the%20Tumor%20Microenvironment&rft.jtitle=Cancers&rft.au=Tsunokake,%20Junichi&rft.date=2022-04-26&rft.volume=14&rft.issue=9&rft.spage=2152&rft.pages=2152-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers14092152&rft_dat=%3Cproquest_pubme%3E2664796028%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2662926459&rft_id=info:pmid/35565281&rfr_iscdi=true |