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VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?
(1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Us...
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| Published in: | Cancers 2022-02, Vol.14 (4), p.1006 |
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| creator | Albertsmeier, Markus Altendorf-Hofmann, Annelore Lindner, Lars H Issels, Rolf D Kampmann, Eric Dürr, Hans-Roland Angele, Martin K Klauschen, Frederick Werner, Jens Jungbluth, Achim A Knösel, Thomas |
| description | (1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Using immunohistochemistry, we examined VISTA expression in tumour tissues of 213 high-risk STS. We then analysed whether VISTA was associated with other clinicopathological parameters, including tumour-infiltrating lymphocyte (TIL) counts, programmed death receptor-1 (PD1), programmed death ligand-1 (PDL1), CD3, grading, and long-term survival. (3) Results: We observed VISTA expression in 96 (45%) of 213 specimens with distinct patterns ranging from 26 to 63% for histological subtypes. VISTA was associated with higher grade (G3 vs. G2,
= 0.019), higher TIL counts (
= 0.033), expression of PD1 (
= 0.046), PDL1 (
= 0.031), and CD3+ (
= 0.023). In patients without CD3
TILs, 10-year survival was higher when VISTA was expressed compared to when there was no VISTA expression (
= 0.013). In a multivariate analysis, VISTA expression was independently associated with prolonged survival (
= 0.043). (4) Conclusions: VISTA is expressed in different STS subtypes and is associated with increased TILs, PD-1, PD-L1, and CD3 expression. Patients with VISTA
tumours show improved survival. These results may help define future immunotherapeutic approaches in STS. |
| doi_str_mv | 10.3390/cancers14041006 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8870227</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2632386427</sourcerecordid><originalsourceid>FETCH-LOGICAL-c421t-f98dbd5ff2e01c6c51842124006f605369c59d77b1f5740517c4d95248a6649b3</originalsourceid><addsrcrecordid>eNpdkUtPAjEUhRujEYKs3ZlJ3LgZ6bszLiSE-CAh0QR025ROK0OYKbYzJPx7B0GC3E1v2q_nnpsDwDWC94SksKdVqY0PiEKKIORnoI2hwDHnKT0_6lugG8ICNkUIElxcghZhGDLBcBv0P0eT6SDKy2jibBVN8xBqE02U165Q4SEaRO_NiJXRVb42kXU-GhVFXbpqbrxabfpX4MKqZTDd_dkBH89P0-FrPH57GQ0H41hTjKrYpkk2y5i12ECkuWYoae4xbWxbDhnhqWZpJsQMWSYoZEhomqUM00RxTtMZ6YDHne6qnhUm06asvFrKlc8L5TfSqVz-fynzufxya5kkAmIsGoG7vYB337UJlSzyoM1yqUrj6iAxJyShAhHaoLcn6MLVvmzW21KYJJz-CvZ2lPYuBG_swQyCcpuPPMmn-XFzvMOB_0uD_AD-3YqE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2632386427</pqid></control><display><type>article</type><title>VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?</title><source>Open Access: PubMed Central</source><source>Publicly Available Content (ProQuest)</source><creator>Albertsmeier, Markus ; Altendorf-Hofmann, Annelore ; Lindner, Lars H ; Issels, Rolf D ; Kampmann, Eric ; Dürr, Hans-Roland ; Angele, Martin K ; Klauschen, Frederick ; Werner, Jens ; Jungbluth, Achim A ; Knösel, Thomas</creator><creatorcontrib>Albertsmeier, Markus ; Altendorf-Hofmann, Annelore ; Lindner, Lars H ; Issels, Rolf D ; Kampmann, Eric ; Dürr, Hans-Roland ; Angele, Martin K ; Klauschen, Frederick ; Werner, Jens ; Jungbluth, Achim A ; Knösel, Thomas</creatorcontrib><description>(1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Using immunohistochemistry, we examined VISTA expression in tumour tissues of 213 high-risk STS. We then analysed whether VISTA was associated with other clinicopathological parameters, including tumour-infiltrating lymphocyte (TIL) counts, programmed death receptor-1 (PD1), programmed death ligand-1 (PDL1), CD3, grading, and long-term survival. (3) Results: We observed VISTA expression in 96 (45%) of 213 specimens with distinct patterns ranging from 26 to 63% for histological subtypes. VISTA was associated with higher grade (G3 vs. G2,
= 0.019), higher TIL counts (
= 0.033), expression of PD1 (
= 0.046), PDL1 (
= 0.031), and CD3+ (
= 0.023). In patients without CD3
TILs, 10-year survival was higher when VISTA was expressed compared to when there was no VISTA expression (
= 0.013). In a multivariate analysis, VISTA expression was independently associated with prolonged survival (
= 0.043). (4) Conclusions: VISTA is expressed in different STS subtypes and is associated with increased TILs, PD-1, PD-L1, and CD3 expression. Patients with VISTA
tumours show improved survival. These results may help define future immunotherapeutic approaches in STS.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14041006</identifier><identifier>PMID: 35205752</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antibodies ; Apoptosis ; Biopsy ; Cancer immunotherapy ; CD3 antigen ; Cell activation ; Chemotherapy ; Heat ; Hyperthermia ; Immunohistochemistry ; Immunotherapy ; Inflammation ; Laboratories ; Liposarcoma ; Lymphocytes T ; Medical prognosis ; Metastasis ; Multivariate analysis ; Pathology ; PD-1 protein ; PD-L1 protein ; Radiation therapy ; Regression analysis ; Sarcoma ; Soft tissue sarcoma ; Statistical analysis ; Surgical outcomes ; Tumors ; Variance analysis</subject><ispartof>Cancers, 2022-02, Vol.14 (4), p.1006</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-c421t-f98dbd5ff2e01c6c51842124006f605369c59d77b1f5740517c4d95248a6649b3</citedby><cites>FETCH-LOGICAL-c421t-f98dbd5ff2e01c6c51842124006f605369c59d77b1f5740517c4d95248a6649b3</cites><orcidid>0000-0002-3494-6561 ; 0000-0002-1822-0197 ; 0000-0002-5028-5062 ; 0000-0003-3708-8264 ; 0000-0002-1347-1173</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2632386427/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2632386427?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25733,27903,27904,36991,36992,44569,53769,53771,74872</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35205752$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Albertsmeier, Markus</creatorcontrib><creatorcontrib>Altendorf-Hofmann, Annelore</creatorcontrib><creatorcontrib>Lindner, Lars H</creatorcontrib><creatorcontrib>Issels, Rolf D</creatorcontrib><creatorcontrib>Kampmann, Eric</creatorcontrib><creatorcontrib>Dürr, Hans-Roland</creatorcontrib><creatorcontrib>Angele, Martin K</creatorcontrib><creatorcontrib>Klauschen, Frederick</creatorcontrib><creatorcontrib>Werner, Jens</creatorcontrib><creatorcontrib>Jungbluth, Achim A</creatorcontrib><creatorcontrib>Knösel, Thomas</creatorcontrib><title>VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>(1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Using immunohistochemistry, we examined VISTA expression in tumour tissues of 213 high-risk STS. We then analysed whether VISTA was associated with other clinicopathological parameters, including tumour-infiltrating lymphocyte (TIL) counts, programmed death receptor-1 (PD1), programmed death ligand-1 (PDL1), CD3, grading, and long-term survival. (3) Results: We observed VISTA expression in 96 (45%) of 213 specimens with distinct patterns ranging from 26 to 63% for histological subtypes. VISTA was associated with higher grade (G3 vs. G2,
= 0.019), higher TIL counts (
= 0.033), expression of PD1 (
= 0.046), PDL1 (
= 0.031), and CD3+ (
= 0.023). In patients without CD3
TILs, 10-year survival was higher when VISTA was expressed compared to when there was no VISTA expression (
= 0.013). In a multivariate analysis, VISTA expression was independently associated with prolonged survival (
= 0.043). (4) Conclusions: VISTA is expressed in different STS subtypes and is associated with increased TILs, PD-1, PD-L1, and CD3 expression. Patients with VISTA
tumours show improved survival. These results may help define future immunotherapeutic approaches in STS.</description><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Biopsy</subject><subject>Cancer immunotherapy</subject><subject>CD3 antigen</subject><subject>Cell activation</subject><subject>Chemotherapy</subject><subject>Heat</subject><subject>Hyperthermia</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Inflammation</subject><subject>Laboratories</subject><subject>Liposarcoma</subject><subject>Lymphocytes T</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Multivariate analysis</subject><subject>Pathology</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Radiation therapy</subject><subject>Regression analysis</subject><subject>Sarcoma</subject><subject>Soft tissue sarcoma</subject><subject>Statistical analysis</subject><subject>Surgical outcomes</subject><subject>Tumors</subject><subject>Variance analysis</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNpdkUtPAjEUhRujEYKs3ZlJ3LgZ6bszLiSE-CAh0QR025ROK0OYKbYzJPx7B0GC3E1v2q_nnpsDwDWC94SksKdVqY0PiEKKIORnoI2hwDHnKT0_6lugG8ICNkUIElxcghZhGDLBcBv0P0eT6SDKy2jibBVN8xBqE02U165Q4SEaRO_NiJXRVb42kXU-GhVFXbpqbrxabfpX4MKqZTDd_dkBH89P0-FrPH57GQ0H41hTjKrYpkk2y5i12ECkuWYoae4xbWxbDhnhqWZpJsQMWSYoZEhomqUM00RxTtMZ6YDHne6qnhUm06asvFrKlc8L5TfSqVz-fynzufxya5kkAmIsGoG7vYB337UJlSzyoM1yqUrj6iAxJyShAhHaoLcn6MLVvmzW21KYJJz-CvZ2lPYuBG_swQyCcpuPPMmn-XFzvMOB_0uD_AD-3YqE</recordid><startdate>20220216</startdate><enddate>20220216</enddate><creator>Albertsmeier, Markus</creator><creator>Altendorf-Hofmann, Annelore</creator><creator>Lindner, Lars H</creator><creator>Issels, Rolf D</creator><creator>Kampmann, Eric</creator><creator>Dürr, Hans-Roland</creator><creator>Angele, Martin K</creator><creator>Klauschen, Frederick</creator><creator>Werner, Jens</creator><creator>Jungbluth, Achim A</creator><creator>Knösel, Thomas</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/0000-0002-3494-6561</orcidid><orcidid>https://orcid.org/0000-0002-1822-0197</orcidid><orcidid>https://orcid.org/0000-0002-5028-5062</orcidid><orcidid>https://orcid.org/0000-0003-3708-8264</orcidid><orcidid>https://orcid.org/0000-0002-1347-1173</orcidid></search><sort><creationdate>20220216</creationdate><title>VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?</title><author>Albertsmeier, Markus ; Altendorf-Hofmann, Annelore ; Lindner, Lars H ; Issels, Rolf D ; Kampmann, Eric ; Dürr, Hans-Roland ; Angele, Martin K ; Klauschen, Frederick ; Werner, Jens ; Jungbluth, Achim A ; Knösel, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-f98dbd5ff2e01c6c51842124006f605369c59d77b1f5740517c4d95248a6649b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Biopsy</topic><topic>Cancer immunotherapy</topic><topic>CD3 antigen</topic><topic>Cell activation</topic><topic>Chemotherapy</topic><topic>Heat</topic><topic>Hyperthermia</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>Inflammation</topic><topic>Laboratories</topic><topic>Liposarcoma</topic><topic>Lymphocytes T</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>Multivariate analysis</topic><topic>Pathology</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Radiation therapy</topic><topic>Regression analysis</topic><topic>Sarcoma</topic><topic>Soft tissue sarcoma</topic><topic>Statistical analysis</topic><topic>Surgical outcomes</topic><topic>Tumors</topic><topic>Variance analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Albertsmeier, Markus</creatorcontrib><creatorcontrib>Altendorf-Hofmann, Annelore</creatorcontrib><creatorcontrib>Lindner, Lars H</creatorcontrib><creatorcontrib>Issels, Rolf D</creatorcontrib><creatorcontrib>Kampmann, Eric</creatorcontrib><creatorcontrib>Dürr, Hans-Roland</creatorcontrib><creatorcontrib>Angele, Martin K</creatorcontrib><creatorcontrib>Klauschen, Frederick</creatorcontrib><creatorcontrib>Werner, Jens</creatorcontrib><creatorcontrib>Jungbluth, Achim A</creatorcontrib><creatorcontrib>Knösel, Thomas</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)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Biological Sciences</collection><collection>ProQuest Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content (ProQuest)</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>Albertsmeier, Markus</au><au>Altendorf-Hofmann, Annelore</au><au>Lindner, Lars H</au><au>Issels, Rolf D</au><au>Kampmann, Eric</au><au>Dürr, Hans-Roland</au><au>Angele, Martin K</au><au>Klauschen, Frederick</au><au>Werner, Jens</au><au>Jungbluth, Achim A</au><au>Knösel, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2022-02-16</date><risdate>2022</risdate><volume>14</volume><issue>4</issue><spage>1006</spage><pages>1006-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>(1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Using immunohistochemistry, we examined VISTA expression in tumour tissues of 213 high-risk STS. We then analysed whether VISTA was associated with other clinicopathological parameters, including tumour-infiltrating lymphocyte (TIL) counts, programmed death receptor-1 (PD1), programmed death ligand-1 (PDL1), CD3, grading, and long-term survival. (3) Results: We observed VISTA expression in 96 (45%) of 213 specimens with distinct patterns ranging from 26 to 63% for histological subtypes. VISTA was associated with higher grade (G3 vs. G2,
= 0.019), higher TIL counts (
= 0.033), expression of PD1 (
= 0.046), PDL1 (
= 0.031), and CD3+ (
= 0.023). In patients without CD3
TILs, 10-year survival was higher when VISTA was expressed compared to when there was no VISTA expression (
= 0.013). In a multivariate analysis, VISTA expression was independently associated with prolonged survival (
= 0.043). (4) Conclusions: VISTA is expressed in different STS subtypes and is associated with increased TILs, PD-1, PD-L1, and CD3 expression. Patients with VISTA
tumours show improved survival. These results may help define future immunotherapeutic approaches in STS.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35205752</pmid><doi>10.3390/cancers14041006</doi><orcidid>https://orcid.org/0000-0002-3494-6561</orcidid><orcidid>https://orcid.org/0000-0002-1822-0197</orcidid><orcidid>https://orcid.org/0000-0002-5028-5062</orcidid><orcidid>https://orcid.org/0000-0003-3708-8264</orcidid><orcidid>https://orcid.org/0000-0002-1347-1173</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies Apoptosis Biopsy Cancer immunotherapy CD3 antigen Cell activation Chemotherapy Heat Hyperthermia Immunohistochemistry Immunotherapy Inflammation Laboratories Liposarcoma Lymphocytes T Medical prognosis Metastasis Multivariate analysis Pathology PD-1 protein PD-L1 protein Radiation therapy Regression analysis Sarcoma Soft tissue sarcoma Statistical analysis Surgical outcomes Tumors Variance analysis |
| title | VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy? |
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