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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/1/272 |
| _version_ | 1797626095858614272 |
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| author | Valentina Evdokimova Hendrik Gassmann Laszlo Radvanyi Stefan E. G. Burdach |
| author_facet | Valentina Evdokimova Hendrik Gassmann Laszlo Radvanyi Stefan E. G. Burdach |
| author_sort | Valentina Evdokimova |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T10:05:37Z |
| format | Article |
| id | doaj.art-28e1c4cea8fc4c2bab95e4aa1c9b15b0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T10:05:37Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-28e1c4cea8fc4c2bab95e4aa1c9b15b02023-11-16T15:03:58ZengMDPI AGCancers2072-66942022-12-0115127210.3390/cancers15010272Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and OsteosarcomaValentina Evdokimova0Hendrik Gassmann1Laszlo Radvanyi2Stefan E. G. Burdach3Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, CanadaDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, TUM School of Medicine, Technical University of Munich, 80804 Munich, GermanyOntario Institute for Cancer Research, Toronto, ON M5G 0A3, CanadaDepartment of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, TUM School of Medicine, Technical University of Munich, 80804 Munich, GermanyWe 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.https://www.mdpi.com/2072-6694/15/1/272Ewing sarcomaosteosarcomaimmunotherapyWilliam Coleytumor microenvironmentextracellular vesicles |
| spellingShingle | Valentina Evdokimova Hendrik Gassmann Laszlo Radvanyi Stefan E. G. Burdach Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma Cancers Ewing sarcoma osteosarcoma immunotherapy William Coley tumor microenvironment extracellular vesicles |
| title | Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma |
| title_full | Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma |
| title_fullStr | Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma |
| title_full_unstemmed | Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma |
| title_short | Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma |
| title_sort | current state of immunotherapy and mechanisms of immune evasion in ewing sarcoma and osteosarcoma |
| topic | Ewing sarcoma osteosarcoma immunotherapy William Coley tumor microenvironment extracellular vesicles |
| url | https://www.mdpi.com/2072-6694/15/1/272 |
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