Enhanced immune responses are accompanied by increased MAGEA expression in osteosarcoma metastases
BMJ Oncology, vol. 3, pp. e000472
Abstract
Objective: Osteosarcoma is the most common primary bone sarcoma. About 50% of patients develop metastatic disease and their 5-year survival lingers at around 20%-30%. T cell checkpoint blockade immunotherapies have revolutionised cancer treatment in the last decade, but their impact remains limited in osteosarcoma. Methods and analysis: In order to reveal potentially novel immunotherapeutic strategies for advanced osteosarcoma, we conducted an immunogenomic characterisation of a unique sample set comprising 30 osteosarcoma samples from seven patients, collected throughout disease progression. We performed RNA-sequencing and imaging mass cytometry analysis on these samples to reveal the immunological landscape during osteosarcoma progression. Results: Transcriptional and phenotypical hallmarks of cytotoxic T cell-driven anticancer immunity were enriched in metastatic lesions as compared with primary tumours. Spatial analysis showed T cells infiltrating central regions of osteosarcoma metastases, indicating the absence of an immune excluded environment. In parallel, we found a pronounced increase in the expression of cancer testis antigens, particularly melanoma antigen family A (MAGEA)-related antigens, in osteosarcoma metastases, which was validated in an independent cohort (N=91). In addition, we demonstrated the presentation of MAGE-derived peptides in three out of four osteosarcoma cell lines. Conclusion: These findings indicate a concurrent augmentation of cytotoxic antitumour immune responses and expression of MAGEA antigens from primary to metastatic osteosarcoma. This observation suggests the exploration of MAGEA antigens as potential targets for immunotherapy in the treatment of advanced osteosarcoma.
Authors 19
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Pathology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Orthopaedic Surgery, Leiden University Medical Center, Leiden, The Netherlands
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Hans A. J. Gelderblom Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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University of Oslo · Leiden University Medical Center
Affiliation as printed
Centre for Molecular Medicine Norway (NCMM), University of Oslo, Oslo, Norway
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
Leiden University Medical Center, Leiden, The Netherlands
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