Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma
Background Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PL...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy : CII Immunotherapy : CII, 2024-03, Vol.73 (5), p.78-78, Article 78 |
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| container_title | Cancer Immunology, Immunotherapy : CII |
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| creator | He, Yijia Liu, Lingyun Dong, Yuexin Zhang, Xiaoxin Song, Yuxian Jing, Yue Ni, Yanhong Wang, Yi Wang, Zhiyong Ding, Liang |
| description | Background
Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC).
Methods
PLIN3 expression patterns (
n
= 87), its immune-related landscape (
n
= 74) and association with B7-H2 (
n
= 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis.
Results
Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3
high
tumor showed high proliferation index with metastasis potential, accompanied with less CD3
+
CD8
+
T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8
+
T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3
high
B7-H2
high
tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285–6.851).
Conclusions
LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC. |
| doi_str_mv | 10.1007/s00262-024-03659-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10981595</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3022575428</sourcerecordid><originalsourceid>FETCH-LOGICAL-c426t-f151bc240039546e18222822106641195cd687346216148d2b0c6c7a9c9e6f483</originalsourceid><addsrcrecordid>eNp9kctOHDEQRa0oCAjwAywiS9mw6VAuP6adTYQQeUgjJYtkbXncnsHQbTd2NxJ_H08GCMkiC8tW1fGturqEnDJ4zwAW5wUAFTaAogGupG70K3LIBK-lVrLXL94H5E0pNwACQet9csBbKQWTeEj6ZRhDR7ucxt5Ppcm-t5Pv6HefQ19bseEf6JgmH6dgexqGYY6eumvvbscU4kRt7GiKLm18rYdIU65YuZvtkOZCne976mx2IabBHpO9te2LP3m8j8jPT1c_Lr80y2-fv15eLBsnUE3Nmkm2cigAuJZCedYiYj0MlBKMaek61S64UMgUE22HK3DKLax22qu1aPkR-bjTHefV4DtXl69bmTGHweYHk2wwf3diuDabdG8Y6JZJLavC2aNCTnezL5MZQtmasdFXX4YDolxIgdth7_5Bb9KcY_W3pQC5YoiVwh3lciol-_XzNgzMNk2zS9PUNM3vNI2un96-9PH85Sm-CvAdUGorbnz-M_s_sr8AA6yqWg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3020236122</pqid></control><display><type>article</type><title>Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma</title><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>SpringerLink Journals - AutoHoldings</source><source>Springer Nature OA Free Journals</source><creator>He, Yijia ; Liu, Lingyun ; Dong, Yuexin ; Zhang, Xiaoxin ; Song, Yuxian ; Jing, Yue ; Ni, Yanhong ; Wang, Yi ; Wang, Zhiyong ; Ding, Liang</creator><creatorcontrib>He, Yijia ; Liu, Lingyun ; Dong, Yuexin ; Zhang, Xiaoxin ; Song, Yuxian ; Jing, Yue ; Ni, Yanhong ; Wang, Yi ; Wang, Zhiyong ; Ding, Liang</creatorcontrib><description>Background
Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC).
Methods
PLIN3 expression patterns (
n
= 87), its immune-related landscape (
n
= 74) and association with B7-H2 (
n
= 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis.
Results
Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3
high
tumor showed high proliferation index with metastasis potential, accompanied with less CD3
+
CD8
+
T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8
+
T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3
high
B7-H2
high
tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285–6.851).
Conclusions
LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.</description><identifier>ISSN: 1432-0851</identifier><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-024-03659-9</identifier><identifier>PMID: 38554152</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Cancer Research ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; CD3 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - metabolism ; Cell activation ; Cell culture ; Cell proliferation ; Flow cytometry ; Head and Neck Neoplasms - metabolism ; Humans ; Immune checkpoint ; Immunofluorescence ; Immunohistochemistry ; Immunology ; Lipid Droplets - metabolism ; Lipid metabolism ; Lipids ; Lymphocytes ; Lymphocytes T ; Medicine ; Medicine & Public Health ; Metastases ; Microenvironments ; Mouth Neoplasms - genetics ; Mouth Neoplasms - metabolism ; Oncogenes ; Oncology ; Oral cancer ; Oral carcinoma ; Oral squamous cell carcinoma ; Organelles ; Perilipin-3 - metabolism ; Peripheral blood ; Squamous cell carcinoma ; Squamous Cell Carcinoma of Head and Neck - metabolism ; Tumor cells ; Tumor Microenvironment ; Tumors</subject><ispartof>Cancer Immunology, Immunotherapy : CII, 2024-03, Vol.73 (5), p.78-78, Article 78</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-c426t-f151bc240039546e18222822106641195cd687346216148d2b0c6c7a9c9e6f483</cites><orcidid>0000-0002-1043-0923</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/PMC10981595/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981595/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41096,41464,42165,42533,51294,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38554152$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Yijia</creatorcontrib><creatorcontrib>Liu, Lingyun</creatorcontrib><creatorcontrib>Dong, Yuexin</creatorcontrib><creatorcontrib>Zhang, Xiaoxin</creatorcontrib><creatorcontrib>Song, Yuxian</creatorcontrib><creatorcontrib>Jing, Yue</creatorcontrib><creatorcontrib>Ni, Yanhong</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Wang, Zhiyong</creatorcontrib><creatorcontrib>Ding, Liang</creatorcontrib><title>Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma</title><title>Cancer Immunology, Immunotherapy : CII</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Background
Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC).
Methods
PLIN3 expression patterns (
n
= 87), its immune-related landscape (
n
= 74) and association with B7-H2 (
n
= 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis.
Results
Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3
high
tumor showed high proliferation index with metastasis potential, accompanied with less CD3
+
CD8
+
T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8
+
T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3
high
B7-H2
high
tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285–6.851).
Conclusions
LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.</description><subject>Cancer Research</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>CD3 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell activation</subject><subject>Cell culture</subject><subject>Cell proliferation</subject><subject>Flow cytometry</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Humans</subject><subject>Immune checkpoint</subject><subject>Immunofluorescence</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Lipid Droplets - metabolism</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Microenvironments</subject><subject>Mouth Neoplasms - genetics</subject><subject>Mouth Neoplasms - metabolism</subject><subject>Oncogenes</subject><subject>Oncology</subject><subject>Oral cancer</subject><subject>Oral carcinoma</subject><subject>Oral squamous cell carcinoma</subject><subject>Organelles</subject><subject>Perilipin-3 - metabolism</subject><subject>Peripheral blood</subject><subject>Squamous cell carcinoma</subject><subject>Squamous Cell Carcinoma of Head and Neck - metabolism</subject><subject>Tumor cells</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><issn>1432-0851</issn><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kctOHDEQRa0oCAjwAywiS9mw6VAuP6adTYQQeUgjJYtkbXncnsHQbTd2NxJ_H08GCMkiC8tW1fGturqEnDJ4zwAW5wUAFTaAogGupG70K3LIBK-lVrLXL94H5E0pNwACQet9csBbKQWTeEj6ZRhDR7ucxt5Ppcm-t5Pv6HefQ19bseEf6JgmH6dgexqGYY6eumvvbscU4kRt7GiKLm18rYdIU65YuZvtkOZCne976mx2IabBHpO9te2LP3m8j8jPT1c_Lr80y2-fv15eLBsnUE3Nmkm2cigAuJZCedYiYj0MlBKMaek61S64UMgUE22HK3DKLax22qu1aPkR-bjTHefV4DtXl69bmTGHweYHk2wwf3diuDabdG8Y6JZJLavC2aNCTnezL5MZQtmasdFXX4YDolxIgdth7_5Bb9KcY_W3pQC5YoiVwh3lciol-_XzNgzMNk2zS9PUNM3vNI2un96-9PH85Sm-CvAdUGorbnz-M_s_sr8AA6yqWg</recordid><startdate>20240330</startdate><enddate>20240330</enddate><creator>He, Yijia</creator><creator>Liu, Lingyun</creator><creator>Dong, Yuexin</creator><creator>Zhang, Xiaoxin</creator><creator>Song, Yuxian</creator><creator>Jing, Yue</creator><creator>Ni, Yanhong</creator><creator>Wang, Yi</creator><creator>Wang, Zhiyong</creator><creator>Ding, Liang</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</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>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1043-0923</orcidid></search><sort><creationdate>20240330</creationdate><title>Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma</title><author>He, Yijia ; Liu, Lingyun ; Dong, Yuexin ; Zhang, Xiaoxin ; Song, Yuxian ; Jing, Yue ; Ni, Yanhong ; Wang, Yi ; Wang, Zhiyong ; Ding, Liang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-f151bc240039546e18222822106641195cd687346216148d2b0c6c7a9c9e6f483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Cancer Research</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>CD3 antigen</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell activation</topic><topic>Cell culture</topic><topic>Cell proliferation</topic><topic>Flow cytometry</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Humans</topic><topic>Immune checkpoint</topic><topic>Immunofluorescence</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Lipid Droplets - metabolism</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Microenvironments</topic><topic>Mouth Neoplasms - genetics</topic><topic>Mouth Neoplasms - metabolism</topic><topic>Oncogenes</topic><topic>Oncology</topic><topic>Oral cancer</topic><topic>Oral carcinoma</topic><topic>Oral squamous cell carcinoma</topic><topic>Organelles</topic><topic>Perilipin-3 - metabolism</topic><topic>Peripheral blood</topic><topic>Squamous cell carcinoma</topic><topic>Squamous Cell Carcinoma of Head and Neck - metabolism</topic><topic>Tumor cells</topic><topic>Tumor Microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Yijia</creatorcontrib><creatorcontrib>Liu, Lingyun</creatorcontrib><creatorcontrib>Dong, Yuexin</creatorcontrib><creatorcontrib>Zhang, Xiaoxin</creatorcontrib><creatorcontrib>Song, Yuxian</creatorcontrib><creatorcontrib>Jing, Yue</creatorcontrib><creatorcontrib>Ni, Yanhong</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Wang, Zhiyong</creatorcontrib><creatorcontrib>Ding, Liang</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy : CII</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Yijia</au><au>Liu, Lingyun</au><au>Dong, Yuexin</au><au>Zhang, Xiaoxin</au><au>Song, Yuxian</au><au>Jing, Yue</au><au>Ni, Yanhong</au><au>Wang, Yi</au><au>Wang, Zhiyong</au><au>Ding, Liang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma</atitle><jtitle>Cancer Immunology, Immunotherapy : CII</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2024-03-30</date><risdate>2024</risdate><volume>73</volume><issue>5</issue><spage>78</spage><epage>78</epage><pages>78-78</pages><artnum>78</artnum><issn>1432-0851</issn><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Background
Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC).
Methods
PLIN3 expression patterns (
n
= 87), its immune-related landscape (
n
= 74) and association with B7-H2 (
n
= 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis.
Results
Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3
high
tumor showed high proliferation index with metastasis potential, accompanied with less CD3
+
CD8
+
T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8
+
T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3
high
B7-H2
high
tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285–6.851).
Conclusions
LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>38554152</pmid><doi>10.1007/s00262-024-03659-9</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-1043-0923</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer Immunology, Immunotherapy : CII, 2024-03, Vol.73 (5), p.78-78, Article 78 |
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| language | eng |
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| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; SpringerLink Journals - AutoHoldings; Springer Nature OA Free Journals |
| subjects | Cancer Research Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism CD3 antigen CD8 antigen CD8-Positive T-Lymphocytes - metabolism Cell activation Cell culture Cell proliferation Flow cytometry Head and Neck Neoplasms - metabolism Humans Immune checkpoint Immunofluorescence Immunohistochemistry Immunology Lipid Droplets - metabolism Lipid metabolism Lipids Lymphocytes Lymphocytes T Medicine Medicine & Public Health Metastases Microenvironments Mouth Neoplasms - genetics Mouth Neoplasms - metabolism Oncogenes Oncology Oral cancer Oral carcinoma Oral squamous cell carcinoma Organelles Perilipin-3 - metabolism Peripheral blood Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - metabolism Tumor cells Tumor Microenvironment Tumors |
| title | Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma |
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