Disruptions in antigen processing and presentation machinery on sarcoma
Background The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detec...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy : CII Immunotherapy : CII, 2024-09, Vol.73 (11), p.228, Article 228 |
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| creator | Renne, Salvatore Lorenzo Sama’, Laura Kumar, Sonia Mintemur, Omer Ruspi, Laura Santori, Ilaria Sicoli, Federico Bertuzzi, Alexia Laffi, Alice Bonometti, Arturo Colombo, Piergiuseppe D’amato, Vittoria Bressan, Alessandra Scorsetti, Marta Terracciano, Luigi Navarria, Pierina D’incalci, Maurizio Quagliuolo, Vittorio Pasqualini, Fabio Grizzi, Fabio Cananzi, Ferdinando Carlo Maria |
| description | Background
The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients.
Methods
We investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001–2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used.
Results
All investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS.
Conclusion
Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches. |
| doi_str_mv | 10.1007/s00262-024-03822-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11383888</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3102211734</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-29e38d4f0d7bbe56a943ed3633a83f132902bdb02a22acf744f40c9836dec383</originalsourceid><addsrcrecordid>eNp9kU1P5DAMhqMVq-XzD3BAlbjspaxjZ9r0hBDLx0pIe-EepWk6BE2TIWmR5t-TYfg-cEpsP35t62XskMMJB6j_JACssAQUJZBELPEH2-GCckrO-NaH_zbbTekeQCA0zS-2TQ2KZlbLHXb116U4LUcXfCqcL7Qf3dz6YhmDsSk5P8-pLoc2WT_qNVcM2tw5b-OqyEHS0YRB77OfvV4ke_Dy7rHby4vb8-vy5v_Vv_Ozm9LQrBpLbCzJTvTQ1W1rZ5VuBNmOKiItqeeEDWDbtYAaUZu-FqIXYBpJVWcNSdpjpxvZ5dQOtjN5p6gXahndoONKBe3U54p3d2oeHhXnuVvKtcLvF4UYHiabRjW4ZOxiob0NU1LEAaGmSlYZPf6C3ocp-nzeM4Wc1yQyhRvKxJBStP3bNhzU2ie18Ulln9SzTwpz09HHO95aXo3JAG2AlEt-buP77G9knwDn9p66</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3102211734</pqid></control><display><type>article</type><title>Disruptions in antigen processing and presentation machinery on sarcoma</title><source>PubMed Central Free</source><source>MEDLINE</source><source>Springer Nature OA Free Journals</source><source>SpringerLink Journals (MCLS)</source><source>Alma/SFX Local Collection</source><creator>Renne, Salvatore Lorenzo ; Sama’, Laura ; Kumar, Sonia ; Mintemur, Omer ; Ruspi, Laura ; Santori, Ilaria ; Sicoli, Federico ; Bertuzzi, Alexia ; Laffi, Alice ; Bonometti, Arturo ; Colombo, Piergiuseppe ; D’amato, Vittoria ; Bressan, Alessandra ; Scorsetti, Marta ; Terracciano, Luigi ; Navarria, Pierina ; D’incalci, Maurizio ; Quagliuolo, Vittorio ; Pasqualini, Fabio ; Grizzi, Fabio ; Cananzi, Ferdinando Carlo Maria</creator><creatorcontrib>Renne, Salvatore Lorenzo ; Sama’, Laura ; Kumar, Sonia ; Mintemur, Omer ; Ruspi, Laura ; Santori, Ilaria ; Sicoli, Federico ; Bertuzzi, Alexia ; Laffi, Alice ; Bonometti, Arturo ; Colombo, Piergiuseppe ; D’amato, Vittoria ; Bressan, Alessandra ; Scorsetti, Marta ; Terracciano, Luigi ; Navarria, Pierina ; D’incalci, Maurizio ; Quagliuolo, Vittorio ; Pasqualini, Fabio ; Grizzi, Fabio ; Cananzi, Ferdinando Carlo Maria</creatorcontrib><description>Background
The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients.
Methods
We investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001–2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used.
Results
All investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS.
Conclusion
Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.</description><identifier>ISSN: 1432-0851</identifier><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-024-03822-2</identifier><identifier>PMID: 39249578</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aged ; Antigen (tumor-associated) ; Antigen presentation ; Antigen Presentation - immunology ; Antigen processing ; Antigens ; Antigens, Neoplasm - immunology ; Antigens, Neoplasm - metabolism ; ATP Binding Cassette Transporter, Subfamily B, Member 3 ; Bayesian analysis ; beta 2-Microglobulin - metabolism ; Cancer Research ; Female ; Histocompatibility antigen HLA ; Humans ; Immune system ; Immunohistochemistry ; Immunology ; Liposarcoma ; Major histocompatibility complex ; Male ; Medicine ; Medicine & Public Health ; Metastases ; Middle Aged ; Molecular modelling ; Oncology ; Prognosis ; Proteasome Endopeptidase Complex - metabolism ; Proteasomes ; Protein arrays ; Sarcoma ; Sarcoma - immunology ; Sarcoma - pathology ; Soft tissue sarcoma ; Tumor cells ; Tumors ; β2 Microglobulin</subject><ispartof>Cancer Immunology, Immunotherapy : CII, 2024-09, Vol.73 (11), p.228, Article 228</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-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-29e38d4f0d7bbe56a943ed3633a83f132902bdb02a22acf744f40c9836dec383</cites><orcidid>0000-0002-0186-1318</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/PMC11383888/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383888/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,41120,41488,42189,42557,51319,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39249578$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Renne, Salvatore Lorenzo</creatorcontrib><creatorcontrib>Sama’, Laura</creatorcontrib><creatorcontrib>Kumar, Sonia</creatorcontrib><creatorcontrib>Mintemur, Omer</creatorcontrib><creatorcontrib>Ruspi, Laura</creatorcontrib><creatorcontrib>Santori, Ilaria</creatorcontrib><creatorcontrib>Sicoli, Federico</creatorcontrib><creatorcontrib>Bertuzzi, Alexia</creatorcontrib><creatorcontrib>Laffi, Alice</creatorcontrib><creatorcontrib>Bonometti, Arturo</creatorcontrib><creatorcontrib>Colombo, Piergiuseppe</creatorcontrib><creatorcontrib>D’amato, Vittoria</creatorcontrib><creatorcontrib>Bressan, Alessandra</creatorcontrib><creatorcontrib>Scorsetti, Marta</creatorcontrib><creatorcontrib>Terracciano, Luigi</creatorcontrib><creatorcontrib>Navarria, Pierina</creatorcontrib><creatorcontrib>D’incalci, Maurizio</creatorcontrib><creatorcontrib>Quagliuolo, Vittorio</creatorcontrib><creatorcontrib>Pasqualini, Fabio</creatorcontrib><creatorcontrib>Grizzi, Fabio</creatorcontrib><creatorcontrib>Cananzi, Ferdinando Carlo Maria</creatorcontrib><title>Disruptions in antigen processing and presentation machinery on sarcoma</title><title>Cancer Immunology, Immunotherapy : CII</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Background
The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients.
Methods
We investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001–2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used.
Results
All investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS.
Conclusion
Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.</description><subject>Adult</subject><subject>Aged</subject><subject>Antigen (tumor-associated)</subject><subject>Antigen presentation</subject><subject>Antigen Presentation - immunology</subject><subject>Antigen processing</subject><subject>Antigens</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Antigens, Neoplasm - metabolism</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 3</subject><subject>Bayesian analysis</subject><subject>beta 2-Microglobulin - metabolism</subject><subject>Cancer Research</subject><subject>Female</subject><subject>Histocompatibility antigen HLA</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunohistochemistry</subject><subject>Immunology</subject><subject>Liposarcoma</subject><subject>Major histocompatibility complex</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Molecular modelling</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Proteasomes</subject><subject>Protein arrays</subject><subject>Sarcoma</subject><subject>Sarcoma - immunology</subject><subject>Sarcoma - pathology</subject><subject>Soft tissue sarcoma</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>β2 Microglobulin</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>eNp9kU1P5DAMhqMVq-XzD3BAlbjspaxjZ9r0hBDLx0pIe-EepWk6BE2TIWmR5t-TYfg-cEpsP35t62XskMMJB6j_JACssAQUJZBELPEH2-GCckrO-NaH_zbbTekeQCA0zS-2TQ2KZlbLHXb116U4LUcXfCqcL7Qf3dz6YhmDsSk5P8-pLoc2WT_qNVcM2tw5b-OqyEHS0YRB77OfvV4ke_Dy7rHby4vb8-vy5v_Vv_Ozm9LQrBpLbCzJTvTQ1W1rZ5VuBNmOKiItqeeEDWDbtYAaUZu-FqIXYBpJVWcNSdpjpxvZ5dQOtjN5p6gXahndoONKBe3U54p3d2oeHhXnuVvKtcLvF4UYHiabRjW4ZOxiob0NU1LEAaGmSlYZPf6C3ocp-nzeM4Wc1yQyhRvKxJBStP3bNhzU2ie18Ulln9SzTwpz09HHO95aXo3JAG2AlEt-buP77G9knwDn9p66</recordid><startdate>20240909</startdate><enddate>20240909</enddate><creator>Renne, Salvatore Lorenzo</creator><creator>Sama’, Laura</creator><creator>Kumar, Sonia</creator><creator>Mintemur, Omer</creator><creator>Ruspi, Laura</creator><creator>Santori, Ilaria</creator><creator>Sicoli, Federico</creator><creator>Bertuzzi, Alexia</creator><creator>Laffi, Alice</creator><creator>Bonometti, Arturo</creator><creator>Colombo, Piergiuseppe</creator><creator>D’amato, Vittoria</creator><creator>Bressan, Alessandra</creator><creator>Scorsetti, Marta</creator><creator>Terracciano, Luigi</creator><creator>Navarria, Pierina</creator><creator>D’incalci, Maurizio</creator><creator>Quagliuolo, Vittorio</creator><creator>Pasqualini, Fabio</creator><creator>Grizzi, Fabio</creator><creator>Cananzi, Ferdinando Carlo Maria</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/0000-0002-0186-1318</orcidid></search><sort><creationdate>20240909</creationdate><title>Disruptions in antigen processing and presentation machinery on sarcoma</title><author>Renne, Salvatore Lorenzo ; Sama’, Laura ; Kumar, Sonia ; Mintemur, Omer ; Ruspi, Laura ; Santori, Ilaria ; Sicoli, Federico ; Bertuzzi, Alexia ; Laffi, Alice ; Bonometti, Arturo ; Colombo, Piergiuseppe ; D’amato, Vittoria ; Bressan, Alessandra ; Scorsetti, Marta ; Terracciano, Luigi ; Navarria, Pierina ; D’incalci, Maurizio ; Quagliuolo, Vittorio ; Pasqualini, Fabio ; Grizzi, Fabio ; Cananzi, Ferdinando Carlo Maria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-29e38d4f0d7bbe56a943ed3633a83f132902bdb02a22acf744f40c9836dec383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antigen (tumor-associated)</topic><topic>Antigen presentation</topic><topic>Antigen Presentation - immunology</topic><topic>Antigen processing</topic><topic>Antigens</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Antigens, Neoplasm - metabolism</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 3</topic><topic>Bayesian analysis</topic><topic>beta 2-Microglobulin - metabolism</topic><topic>Cancer Research</topic><topic>Female</topic><topic>Histocompatibility antigen HLA</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Liposarcoma</topic><topic>Major histocompatibility complex</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Molecular modelling</topic><topic>Oncology</topic><topic>Prognosis</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Proteasomes</topic><topic>Protein arrays</topic><topic>Sarcoma</topic><topic>Sarcoma - immunology</topic><topic>Sarcoma - pathology</topic><topic>Soft tissue sarcoma</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>β2 Microglobulin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Renne, Salvatore Lorenzo</creatorcontrib><creatorcontrib>Sama’, Laura</creatorcontrib><creatorcontrib>Kumar, Sonia</creatorcontrib><creatorcontrib>Mintemur, Omer</creatorcontrib><creatorcontrib>Ruspi, Laura</creatorcontrib><creatorcontrib>Santori, Ilaria</creatorcontrib><creatorcontrib>Sicoli, Federico</creatorcontrib><creatorcontrib>Bertuzzi, Alexia</creatorcontrib><creatorcontrib>Laffi, Alice</creatorcontrib><creatorcontrib>Bonometti, Arturo</creatorcontrib><creatorcontrib>Colombo, Piergiuseppe</creatorcontrib><creatorcontrib>D’amato, Vittoria</creatorcontrib><creatorcontrib>Bressan, Alessandra</creatorcontrib><creatorcontrib>Scorsetti, Marta</creatorcontrib><creatorcontrib>Terracciano, Luigi</creatorcontrib><creatorcontrib>Navarria, Pierina</creatorcontrib><creatorcontrib>D’incalci, Maurizio</creatorcontrib><creatorcontrib>Quagliuolo, Vittorio</creatorcontrib><creatorcontrib>Pasqualini, Fabio</creatorcontrib><creatorcontrib>Grizzi, Fabio</creatorcontrib><creatorcontrib>Cananzi, Ferdinando Carlo Maria</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>Renne, Salvatore Lorenzo</au><au>Sama’, Laura</au><au>Kumar, Sonia</au><au>Mintemur, Omer</au><au>Ruspi, Laura</au><au>Santori, Ilaria</au><au>Sicoli, Federico</au><au>Bertuzzi, Alexia</au><au>Laffi, Alice</au><au>Bonometti, Arturo</au><au>Colombo, Piergiuseppe</au><au>D’amato, Vittoria</au><au>Bressan, Alessandra</au><au>Scorsetti, Marta</au><au>Terracciano, Luigi</au><au>Navarria, Pierina</au><au>D’incalci, Maurizio</au><au>Quagliuolo, Vittorio</au><au>Pasqualini, Fabio</au><au>Grizzi, Fabio</au><au>Cananzi, Ferdinando Carlo Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Disruptions in antigen processing and presentation machinery on sarcoma</atitle><jtitle>Cancer Immunology, Immunotherapy : CII</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2024-09-09</date><risdate>2024</risdate><volume>73</volume><issue>11</issue><spage>228</spage><pages>228-</pages><artnum>228</artnum><issn>1432-0851</issn><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Background
The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients.
Methods
We investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001–2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used.
Results
All investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS.
Conclusion
Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>39249578</pmid><doi>10.1007/s00262-024-03822-2</doi><orcidid>https://orcid.org/0000-0002-0186-1318</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Antigen (tumor-associated) Antigen presentation Antigen Presentation - immunology Antigen processing Antigens Antigens, Neoplasm - immunology Antigens, Neoplasm - metabolism ATP Binding Cassette Transporter, Subfamily B, Member 3 Bayesian analysis beta 2-Microglobulin - metabolism Cancer Research Female Histocompatibility antigen HLA Humans Immune system Immunohistochemistry Immunology Liposarcoma Major histocompatibility complex Male Medicine Medicine & Public Health Metastases Middle Aged Molecular modelling Oncology Prognosis Proteasome Endopeptidase Complex - metabolism Proteasomes Protein arrays Sarcoma Sarcoma - immunology Sarcoma - pathology Soft tissue sarcoma Tumor cells Tumors β2 Microglobulin |
| title | Disruptions in antigen processing and presentation machinery on sarcoma |
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