Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?
Sarcomas comprise a collection of highly heterogeneous malignancies that can be grossly grouped in the categories of sarcomas with simple or complex genomes. Since the outcome for most sarcoma patients has barely improved in the last decades, there is an urgent need for improved therapies. Immunothe...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/9/8/1048 |
| _version_ | 1827685810118328320 |
|---|---|
| author | Siddh van Oost Debora M. Meijer Marieke L. Kuijjer Judith V. M. G. Bovée Noel F. C. C. de Miranda |
| author_facet | Siddh van Oost Debora M. Meijer Marieke L. Kuijjer Judith V. M. G. Bovée Noel F. C. C. de Miranda |
| author_sort | Siddh van Oost |
| collection | DOAJ |
| description | Sarcomas comprise a collection of highly heterogeneous malignancies that can be grossly grouped in the categories of sarcomas with simple or complex genomes. Since the outcome for most sarcoma patients has barely improved in the last decades, there is an urgent need for improved therapies. Immunotherapy, and especially T cell checkpoint blockade, has recently been a game-changer in cancer therapy as it produced significant and durable treatment responses in several cancer types. Currently, only a small fraction of sarcoma patients benefit from immunotherapy, supposedly due to a general lack of somatically mutated antigens (neoantigens) and spontaneous T cell immunity in most cancers. However, genomic events resulting from chromosomal instability are frequent in sarcomas with complex genomes and could drive immunity in those tumors. Improving our understanding of the mechanisms that shape the immune landscape of sarcomas will be crucial to overcoming the current challenges of sarcoma immunotherapy. This review focuses on what is currently known about the tumor microenvironment in sarcomas and how this relates to their genomic features. Moreover, we discuss novel therapeutic strategies that leverage the tumor microenvironment to increase the clinical efficacy of immunotherapy, and which could provide new avenues for the treatment of sarcomas. |
| first_indexed | 2024-03-10T08:59:43Z |
| format | Article |
| id | doaj.art-b800d3b31ea04fa9b54d18fd00037904 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T08:59:43Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-b800d3b31ea04fa9b54d18fd000379042023-11-22T06:53:52ZengMDPI AGBiomedicines2227-90592021-08-0198104810.3390/biomedicines9081048Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?Siddh van Oost0Debora M. Meijer1Marieke L. Kuijjer2Judith V. M. G. Bovée3Noel F. C. C. de Miranda4Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsSarcomas comprise a collection of highly heterogeneous malignancies that can be grossly grouped in the categories of sarcomas with simple or complex genomes. Since the outcome for most sarcoma patients has barely improved in the last decades, there is an urgent need for improved therapies. Immunotherapy, and especially T cell checkpoint blockade, has recently been a game-changer in cancer therapy as it produced significant and durable treatment responses in several cancer types. Currently, only a small fraction of sarcoma patients benefit from immunotherapy, supposedly due to a general lack of somatically mutated antigens (neoantigens) and spontaneous T cell immunity in most cancers. However, genomic events resulting from chromosomal instability are frequent in sarcomas with complex genomes and could drive immunity in those tumors. Improving our understanding of the mechanisms that shape the immune landscape of sarcomas will be crucial to overcoming the current challenges of sarcoma immunotherapy. This review focuses on what is currently known about the tumor microenvironment in sarcomas and how this relates to their genomic features. Moreover, we discuss novel therapeutic strategies that leverage the tumor microenvironment to increase the clinical efficacy of immunotherapy, and which could provide new avenues for the treatment of sarcomas.https://www.mdpi.com/2227-9059/9/8/1048sarcomagenomicsheterogeneitycheckpoint blockadetumor microenvironmentimmunotherapy |
| spellingShingle | Siddh van Oost Debora M. Meijer Marieke L. Kuijjer Judith V. M. G. Bovée Noel F. C. C. de Miranda Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger? Biomedicines sarcoma genomics heterogeneity checkpoint blockade tumor microenvironment immunotherapy |
| title | Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger? |
| title_full | Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger? |
| title_fullStr | Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger? |
| title_full_unstemmed | Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger? |
| title_short | Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger? |
| title_sort | linking immunity with genomics in sarcomas is genomic complexity an immunogenic trigger |
| topic | sarcoma genomics heterogeneity checkpoint blockade tumor microenvironment immunotherapy |
| url | https://www.mdpi.com/2227-9059/9/8/1048 |
| work_keys_str_mv | AT siddhvanoost linkingimmunitywithgenomicsinsarcomasisgenomiccomplexityanimmunogenictrigger AT deborammeijer linkingimmunitywithgenomicsinsarcomasisgenomiccomplexityanimmunogenictrigger AT mariekelkuijjer linkingimmunitywithgenomicsinsarcomasisgenomiccomplexityanimmunogenictrigger AT judithvmgbovee linkingimmunitywithgenomicsinsarcomasisgenomiccomplexityanimmunogenictrigger AT noelfccdemiranda linkingimmunitywithgenomicsinsarcomasisgenomiccomplexityanimmunogenictrigger |