Deciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS study
Abstract Metabolic elevation in soft-tissue sarcomas (STS), as documented with 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) has been linked with cell proliferation, higher grade, and lower survivals. However, the recent diagnostic innovations (CINSARC gene-expression signatur...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Biomarker Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40364-023-00552-y |
| _version_ | 1797355647347458048 |
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| author | Amandine Crombé Frédéric Bertolo Lucile Vanhersecke Jean-Philippe Guegan Alban Bessede Raul Perret François Le Loarer Vanessa Chaire Jean-Michel Coindre Carlo Lucchesi Antoine Italiano |
| author_facet | Amandine Crombé Frédéric Bertolo Lucile Vanhersecke Jean-Philippe Guegan Alban Bessede Raul Perret François Le Loarer Vanessa Chaire Jean-Michel Coindre Carlo Lucchesi Antoine Italiano |
| author_sort | Amandine Crombé |
| collection | DOAJ |
| description | Abstract Metabolic elevation in soft-tissue sarcomas (STS), as documented with 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) has been linked with cell proliferation, higher grade, and lower survivals. However, the recent diagnostic innovations (CINSARC gene-expression signature and tertiary lymphoid structure [TLS]) and therapeutic innovations (immune checkpoint inhibitors [ICIs]) for STS patients underscore the need to re-assess the role of 18F-FDG-PET/CT. Thus, in this correspondence, our objective was to investigate the correlations between STS metabolism as assessed by nuclear imaging, and the immune landscape as estimated by transcriptomics analysis, immunohistochemistry panels, and TLS assessment. Based on a prospective cohort of 85 adult patients with high-grade STS recruited in the NEOSARCOMICS trial (NCT02789384), we identified 3 metabolic groups according to 18F-FDG-PET/CT metrics (metabolic-low [60%], -intermediate [15.3%] and high [24.7%]). We found that T-cells CD8 pathway was significantly enriched in metabolic-high STS. Conversely, several pathways involved in antitumor immune response, cell differentiation and cell cycle, were downregulated in extreme metabolic-low STS. Next, multiplex immunofluorescence showed that densities of CD8+, CD14+, CD45+, CD68+, and c-MAF cells were significantly higher in the metabolic-high group compared to the metabolic-low group. Lastly, no association was found between metabolic group and TLS status. Overall, these results suggest that (i) rapidly proliferating and metabolically active STS can instigate a more robust immune response, thereby attracting immune cells such as T cells and macrophages, and (ii) metabolic activity and TLS could independently influence immune responses. |
| first_indexed | 2024-03-08T14:14:09Z |
| format | Article |
| id | doaj.art-65453d536dd54f6884de4ead08e0859a |
| institution | Directory Open Access Journal |
| issn | 2050-7771 |
| language | English |
| last_indexed | 2024-03-08T14:14:09Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj.art-65453d536dd54f6884de4ead08e0859a2024-01-14T12:30:55ZengBMCBiomarker Research2050-77712024-01-011211510.1186/s40364-023-00552-yDeciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS studyAmandine Crombé0Frédéric Bertolo1Lucile Vanhersecke2Jean-Philippe Guegan3Alban Bessede4Raul Perret5François Le Loarer6Vanessa Chaire7Jean-Michel Coindre8Carlo Lucchesi9Antoine Italiano10Department of Oncologic Imaging, Comprehensive Cancer Center, Institut BergoniéDepartment of Bioinformatics, Comprehensive Cancer Center, Institut BergoniéDepartment of Pathology, Comprehensive Cancer Center, Institut BergoniéExplicyteExplicyteDepartment of Pathology, Comprehensive Cancer Center, Institut BergoniéSARCOTARGET Team, Bordeaux Institute of Oncology (BRIC) INSERM U1312SARCOTARGET Team, Bordeaux Institute of Oncology (BRIC) INSERM U1312SARCOTARGET Team, Bordeaux Institute of Oncology (BRIC) INSERM U1312Department of Bioinformatics, Comprehensive Cancer Center, Institut BergoniéSARCOTARGET Team, Bordeaux Institute of Oncology (BRIC) INSERM U1312Abstract Metabolic elevation in soft-tissue sarcomas (STS), as documented with 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) has been linked with cell proliferation, higher grade, and lower survivals. However, the recent diagnostic innovations (CINSARC gene-expression signature and tertiary lymphoid structure [TLS]) and therapeutic innovations (immune checkpoint inhibitors [ICIs]) for STS patients underscore the need to re-assess the role of 18F-FDG-PET/CT. Thus, in this correspondence, our objective was to investigate the correlations between STS metabolism as assessed by nuclear imaging, and the immune landscape as estimated by transcriptomics analysis, immunohistochemistry panels, and TLS assessment. Based on a prospective cohort of 85 adult patients with high-grade STS recruited in the NEOSARCOMICS trial (NCT02789384), we identified 3 metabolic groups according to 18F-FDG-PET/CT metrics (metabolic-low [60%], -intermediate [15.3%] and high [24.7%]). We found that T-cells CD8 pathway was significantly enriched in metabolic-high STS. Conversely, several pathways involved in antitumor immune response, cell differentiation and cell cycle, were downregulated in extreme metabolic-low STS. Next, multiplex immunofluorescence showed that densities of CD8+, CD14+, CD45+, CD68+, and c-MAF cells were significantly higher in the metabolic-high group compared to the metabolic-low group. Lastly, no association was found between metabolic group and TLS status. Overall, these results suggest that (i) rapidly proliferating and metabolically active STS can instigate a more robust immune response, thereby attracting immune cells such as T cells and macrophages, and (ii) metabolic activity and TLS could independently influence immune responses.https://doi.org/10.1186/s40364-023-00552-ySoft-tissue sarcoma18F-FDG-PET/CTTranscriptomicsDifferential gene expressionImmune landscape |
| spellingShingle | Amandine Crombé Frédéric Bertolo Lucile Vanhersecke Jean-Philippe Guegan Alban Bessede Raul Perret François Le Loarer Vanessa Chaire Jean-Michel Coindre Carlo Lucchesi Antoine Italiano Deciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS study Biomarker Research Soft-tissue sarcoma 18F-FDG-PET/CT Transcriptomics Differential gene expression Immune landscape |
| title | Deciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS study |
| title_full | Deciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS study |
| title_fullStr | Deciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS study |
| title_full_unstemmed | Deciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS study |
| title_short | Deciphering the correlation between metabolic activity through 18F-FDG-PET/CT and immune landscape in soft-tissue sarcomas: an insight from the NEOSARCOMICS study |
| title_sort | deciphering the correlation between metabolic activity through 18f fdg pet ct and immune landscape in soft tissue sarcomas an insight from the neosarcomics study |
| topic | Soft-tissue sarcoma 18F-FDG-PET/CT Transcriptomics Differential gene expression Immune landscape |
| url | https://doi.org/10.1186/s40364-023-00552-y |
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