Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma
We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first types of tumors treat...
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| Veröffentlicht in: | Cancers 2022-12, Vol.15 (1), p.272 |
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| creator | Evdokimova, Valentina Gassmann, Hendrik Radvanyi, Laszlo Burdach, Stefan E G |
| description | We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first types of tumors treated with the immunotherapy approach: more than 100 years ago American surgeon William B. Coley injected his patients with a mixture of heat-inactivated bacteria, achieving survival rates apparently higher than with surgery alone. In contrast to OS which exhibits recurrent somatic copy-number alterations, EwS possesses one of the lowest mutation rates among cancers, being driven by a single oncogenic fusion protein, most frequently EWS-FLI1. In spite these differences, both EwS and OS are allied with immune tolerance and low immunogenicity. We discuss here the potential mechanisms of immune escape in these tumors, including low representation of tumor-specific antigens, low expression levels of MHC-I antigen-presenting molecules, accumulation of immunosuppressive M2 macrophages and myeloid proinflammatory cells, and release of extracellular vesicles (EVs) which are capable of reprogramming host cells in the tumor microenvironment and systemic circulation. We also discuss the vulnerabilities of EwS and OS and potential novel strategies for their targeting. |
| doi_str_mv | 10.3390/cancers15010272 |
| format | Article |
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From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first types of tumors treated with the immunotherapy approach: more than 100 years ago American surgeon William B. Coley injected his patients with a mixture of heat-inactivated bacteria, achieving survival rates apparently higher than with surgery alone. In contrast to OS which exhibits recurrent somatic copy-number alterations, EwS possesses one of the lowest mutation rates among cancers, being driven by a single oncogenic fusion protein, most frequently EWS-FLI1. In spite these differences, both EwS and OS are allied with immune tolerance and low immunogenicity. We discuss here the potential mechanisms of immune escape in these tumors, including low representation of tumor-specific antigens, low expression levels of MHC-I antigen-presenting molecules, accumulation of immunosuppressive M2 macrophages and myeloid proinflammatory cells, and release of extracellular vesicles (EVs) which are capable of reprogramming host cells in the tumor microenvironment and systemic circulation. We also discuss the vulnerabilities of EwS and OS and potential novel strategies for their targeting.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15010272</identifier><identifier>PMID: 36612267</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antigen (tumor-associated) ; Bacteria ; Bladder cancer ; Body temperature ; Bone tumors ; Cancer therapies ; Care and treatment ; Chemotherapy ; Clinical medicine ; Clinical trials ; Drug dosages ; Epigenetics ; Ewing's sarcoma ; Ewings sarcoma ; Fever ; Forecasts and trends ; Fusion protein ; Gene expression ; Hospitals ; Immune evasion ; Immunogenicity ; Immunological tolerance ; Immunosuppression ; Immunotherapy ; Inflammation ; Kinases ; Lymphocytes ; Macrophages ; Major histocompatibility complex ; Malignancy ; Metastasis ; Methods ; Mutation ; Mutation rates ; Osteosarcoma ; Patients ; Pediatrics ; Radiation ; Review ; Toxins ; Tumor microenvironment ; Tumors ; Vaccines</subject><ispartof>Cancers, 2022-12, Vol.15 (1), p.272</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><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/). 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We discuss here the potential mechanisms of immune escape in these tumors, including low representation of tumor-specific antigens, low expression levels of MHC-I antigen-presenting molecules, accumulation of immunosuppressive M2 macrophages and myeloid proinflammatory cells, and release of extracellular vesicles (EVs) which are capable of reprogramming host cells in the tumor microenvironment and systemic circulation. We also discuss the vulnerabilities of EwS and OS and potential novel strategies for their targeting.</description><subject>Antigen (tumor-associated)</subject><subject>Bacteria</subject><subject>Bladder cancer</subject><subject>Body temperature</subject><subject>Bone tumors</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Chemotherapy</subject><subject>Clinical medicine</subject><subject>Clinical trials</subject><subject>Drug dosages</subject><subject>Epigenetics</subject><subject>Ewing's sarcoma</subject><subject>Ewings sarcoma</subject><subject>Fever</subject><subject>Forecasts and trends</subject><subject>Fusion protein</subject><subject>Gene expression</subject><subject>Hospitals</subject><subject>Immune evasion</subject><subject>Immunogenicity</subject><subject>Immunological tolerance</subject><subject>Immunosuppression</subject><subject>Immunotherapy</subject><subject>Inflammation</subject><subject>Kinases</subject><subject>Lymphocytes</subject><subject>Macrophages</subject><subject>Major histocompatibility complex</subject><subject>Malignancy</subject><subject>Metastasis</subject><subject>Methods</subject><subject>Mutation</subject><subject>Mutation rates</subject><subject>Osteosarcoma</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Radiation</subject><subject>Review</subject><subject>Toxins</subject><subject>Tumor microenvironment</subject><subject>Tumors</subject><subject>Vaccines</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>eNptkk1PGzEQhq2qVUGBM7fKUi-9BPy1_rhUQlFakKg4UM6W12snRrt2au9S8e_rEEgBYR88mnneGb3WAHCC0SmlCp1ZE63LBTcIIyLIB3BIkCBzzhX7-CI-AMel3KF6KMWCi8_ggHKOCeHiEJjFlLOLI7wZzehg8vByGKaYxrXLZvMATezgL2fXJoYylH3dweW9KSFFGCJc_g1xBW9Mtmkwj4rrMrpUdokj8Mmbvrjjp3cGbn8sfy8u5lfXPy8X51dzy6Qc50ooThRlErcNMbhRjLVOIkUt6hpVHTqiWMeQ594TjJEQTYO6tvMtRpIxTGfg-67vZmoH19lqKpteb3IYTH7QyQT9uhLDWq_SvVYSS1xHz8C3pwY5_ZlcGfUQinV9b6JLU9FEcKyE4JJX9Osb9C5NOVZ7jxRSkin6n1qZ3ukQfapz7bapPhesIYI2ZEudvkPV27kh2BSdDzX_SnC2E9icSsnO7z1ipLeLod8sRlV8efk1e_55Deg_YcOyxQ</recordid><startdate>20221230</startdate><enddate>20221230</enddate><creator>Evdokimova, Valentina</creator><creator>Gassmann, Hendrik</creator><creator>Radvanyi, Laszlo</creator><creator>Burdach, Stefan E G</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/0000-0003-2503-4912</orcidid><orcidid>https://orcid.org/0000-0001-6400-4471</orcidid><orcidid>https://orcid.org/0000-0003-1603-3547</orcidid></search><sort><creationdate>20221230</creationdate><title>Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma</title><author>Evdokimova, Valentina ; Gassmann, Hendrik ; Radvanyi, Laszlo ; Burdach, Stefan E G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-9796293481b52a15944be8093c0d59010e294d40f6ff211077550dbdfb1084413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antigen (tumor-associated)</topic><topic>Bacteria</topic><topic>Bladder cancer</topic><topic>Body temperature</topic><topic>Bone tumors</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Chemotherapy</topic><topic>Clinical medicine</topic><topic>Clinical trials</topic><topic>Drug dosages</topic><topic>Epigenetics</topic><topic>Ewing's sarcoma</topic><topic>Ewings sarcoma</topic><topic>Fever</topic><topic>Forecasts and trends</topic><topic>Fusion protein</topic><topic>Gene expression</topic><topic>Hospitals</topic><topic>Immune evasion</topic><topic>Immunogenicity</topic><topic>Immunological tolerance</topic><topic>Immunosuppression</topic><topic>Immunotherapy</topic><topic>Inflammation</topic><topic>Kinases</topic><topic>Lymphocytes</topic><topic>Macrophages</topic><topic>Major histocompatibility complex</topic><topic>Malignancy</topic><topic>Metastasis</topic><topic>Methods</topic><topic>Mutation</topic><topic>Mutation rates</topic><topic>Osteosarcoma</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Radiation</topic><topic>Review</topic><topic>Toxins</topic><topic>Tumor microenvironment</topic><topic>Tumors</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Evdokimova, Valentina</creatorcontrib><creatorcontrib>Gassmann, Hendrik</creatorcontrib><creatorcontrib>Radvanyi, Laszlo</creatorcontrib><creatorcontrib>Burdach, Stefan E G</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>Evdokimova, Valentina</au><au>Gassmann, Hendrik</au><au>Radvanyi, Laszlo</au><au>Burdach, Stefan E G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2022-12-30</date><risdate>2022</risdate><volume>15</volume><issue>1</issue><spage>272</spage><pages>272-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first types of tumors treated with the immunotherapy approach: more than 100 years ago American surgeon William B. Coley injected his patients with a mixture of heat-inactivated bacteria, achieving survival rates apparently higher than with surgery alone. In contrast to OS which exhibits recurrent somatic copy-number alterations, EwS possesses one of the lowest mutation rates among cancers, being driven by a single oncogenic fusion protein, most frequently EWS-FLI1. In spite these differences, both EwS and OS are allied with immune tolerance and low immunogenicity. We discuss here the potential mechanisms of immune escape in these tumors, including low representation of tumor-specific antigens, low expression levels of MHC-I antigen-presenting molecules, accumulation of immunosuppressive M2 macrophages and myeloid proinflammatory cells, and release of extracellular vesicles (EVs) which are capable of reprogramming host cells in the tumor microenvironment and systemic circulation. We also discuss the vulnerabilities of EwS and OS and potential novel strategies for their targeting.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36612267</pmid><doi>10.3390/cancers15010272</doi><orcidid>https://orcid.org/0000-0003-2503-4912</orcidid><orcidid>https://orcid.org/0000-0001-6400-4471</orcidid><orcidid>https://orcid.org/0000-0003-1603-3547</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antigen (tumor-associated) Bacteria Bladder cancer Body temperature Bone tumors Cancer therapies Care and treatment Chemotherapy Clinical medicine Clinical trials Drug dosages Epigenetics Ewing's sarcoma Ewings sarcoma Fever Forecasts and trends Fusion protein Gene expression Hospitals Immune evasion Immunogenicity Immunological tolerance Immunosuppression Immunotherapy Inflammation Kinases Lymphocytes Macrophages Major histocompatibility complex Malignancy Metastasis Methods Mutation Mutation rates Osteosarcoma Patients Pediatrics Radiation Review Toxins Tumor microenvironment Tumors Vaccines |
| title | Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma |
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