Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy
Background: Anthracycline-based neoadjuvant chemotherapy (NAC) may modify tumour immune infiltrate. This study characterized immune infiltrate spatial distribution after NAC in primary high-risk soft tissue sarcomas (STS) and investigate association with prognosis. Methods: The ISG-STS 1001 trial ra...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:299788 |
| Acceso en línea: | https://ddd.uab.cat/record/299788 https://dx.doi.org/urn:doi:10.1016/j.ebiom.2024.105220 |
| Access Level: | acceso abierto |
| Palabra clave: | Anthracycline Neoadjuvant chemotherapy Soft tissue sarcomas Tumour immune microenvironment |
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Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapyPasquali, Sandro|||0000-0003-4815-6293Vallacchi, Viviana|||0000-0002-2819-0630Lalli, Luca|||0000-0002-4472-628XCollini, Paola|||0000-0002-6158-210XBarisella, Marta|||0000-0001-9728-3120Romagosa, CleoféBagué Rosell, Sílvia|||0000-0001-9980-7231Coindre, Jean Michel|||0000-0001-8039-6786Dei Tos, Angelo|||0000-0002-1228-8940Palmerini, Emanuela|||0000-0003-3406-6705Quagliuolo, VittorioMartín-Broto, Javier|||0000-0001-7350-6916López Pousa, AntonioGrignani, Giovanni|||0000-0001-5515-569XBlay, Jean-Yves|||0000-0001-7190-120XDiaz Beveridge, RobertCasiraghi, ElenaBrich, Silvia|||0000-0002-6359-1712Renne, Salvatore LorenzoBergamaschi, LauraVergani, BarbaraSbaraglia, MartaCasali, Paolo Giovanni|||0000-0003-4056-8023Rivoltini, LiciaStacchiotti, Silvia|||0000-0002-1742-8666Gronchi, Alessandro|||0000-0002-4703-3534AnthracyclineNeoadjuvant chemotherapySoft tissue sarcomasTumour immune microenvironmentBackground: Anthracycline-based neoadjuvant chemotherapy (NAC) may modify tumour immune infiltrate. This study characterized immune infiltrate spatial distribution after NAC in primary high-risk soft tissue sarcomas (STS) and investigate association with prognosis. Methods: The ISG-STS 1001 trial randomized STS patients to anthracycline plus ifosfamide (AI) or a histology-tailored (HT) NAC. Four areas of tumour specimens were sampled: the area showing the highest lymphocyte infiltrate (HI) at H&E; the area with lack of post-treatment changes (highest grade, HG); the area with post-treatment changes (lowest grade, LG); and the tumour edge (TE). CD3, CD8, PD-1, CD20, FOXP3, and CD163 were analyzed at immunohistochemistry and digital pathology. A machine learning method was used to generate sarcoma immune index scores (SIS) that predict patient disease-free and overall survival (DFS and OS). Findings: Tumour infiltrating lymphocytes and PD-1+ cells together with CD163+ cells were more represented in STS histologies with complex compared to simple karyotype, while CD20+ B-cells were detected in both these histology groups. PD-1+ cells exerted a negative prognostic value irrespectively of their spatial distribution. Enrichment in CD20+ B-cells at HI and TE areas was associated with better patient outcomes. We generated a prognostic SIS for each tumour area, having the HI-SIS the best performance. Such prognostic value was driven by treatment with AI. Interpretation: The different spatial distribution of immune populations and their different association with prognosis support NAC as a modifier of tumour immune infiltrate in STS.Universitat Autònoma de Barcelona 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/299788https://dx.doi.org/urn:doi:10.1016/j.ebiom.2024.105220reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2997882026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy |
| title |
Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy |
| spellingShingle |
Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy Pasquali, Sandro|||0000-0003-4815-6293 Anthracycline Neoadjuvant chemotherapy Soft tissue sarcomas Tumour immune microenvironment |
| title_short |
Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy |
| title_full |
Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy |
| title_fullStr |
Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy |
| title_full_unstemmed |
Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy |
| title_sort |
Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy |
| dc.creator.none.fl_str_mv |
Pasquali, Sandro|||0000-0003-4815-6293 Vallacchi, Viviana|||0000-0002-2819-0630 Lalli, Luca|||0000-0002-4472-628X Collini, Paola|||0000-0002-6158-210X Barisella, Marta|||0000-0001-9728-3120 Romagosa, Cleofé Bagué Rosell, Sílvia|||0000-0001-9980-7231 Coindre, Jean Michel|||0000-0001-8039-6786 Dei Tos, Angelo|||0000-0002-1228-8940 Palmerini, Emanuela|||0000-0003-3406-6705 Quagliuolo, Vittorio Martín-Broto, Javier|||0000-0001-7350-6916 López Pousa, Antonio Grignani, Giovanni|||0000-0001-5515-569X Blay, Jean-Yves|||0000-0001-7190-120X Diaz Beveridge, Robert Casiraghi, Elena Brich, Silvia|||0000-0002-6359-1712 Renne, Salvatore Lorenzo Bergamaschi, Laura Vergani, Barbara Sbaraglia, Marta Casali, Paolo Giovanni|||0000-0003-4056-8023 Rivoltini, Licia Stacchiotti, Silvia|||0000-0002-1742-8666 Gronchi, Alessandro|||0000-0002-4703-3534 |
| author |
Pasquali, Sandro|||0000-0003-4815-6293 |
| author_facet |
Pasquali, Sandro|||0000-0003-4815-6293 Vallacchi, Viviana|||0000-0002-2819-0630 Lalli, Luca|||0000-0002-4472-628X Collini, Paola|||0000-0002-6158-210X Barisella, Marta|||0000-0001-9728-3120 Romagosa, Cleofé Bagué Rosell, Sílvia|||0000-0001-9980-7231 Coindre, Jean Michel|||0000-0001-8039-6786 Dei Tos, Angelo|||0000-0002-1228-8940 Palmerini, Emanuela|||0000-0003-3406-6705 Quagliuolo, Vittorio Martín-Broto, Javier|||0000-0001-7350-6916 López Pousa, Antonio Grignani, Giovanni|||0000-0001-5515-569X Blay, Jean-Yves|||0000-0001-7190-120X Diaz Beveridge, Robert Casiraghi, Elena Brich, Silvia|||0000-0002-6359-1712 Renne, Salvatore Lorenzo Bergamaschi, Laura Vergani, Barbara Sbaraglia, Marta Casali, Paolo Giovanni|||0000-0003-4056-8023 Rivoltini, Licia Stacchiotti, Silvia|||0000-0002-1742-8666 Gronchi, Alessandro|||0000-0002-4703-3534 |
| author_role |
author |
| author2 |
Vallacchi, Viviana|||0000-0002-2819-0630 Lalli, Luca|||0000-0002-4472-628X Collini, Paola|||0000-0002-6158-210X Barisella, Marta|||0000-0001-9728-3120 Romagosa, Cleofé Bagué Rosell, Sílvia|||0000-0001-9980-7231 Coindre, Jean Michel|||0000-0001-8039-6786 Dei Tos, Angelo|||0000-0002-1228-8940 Palmerini, Emanuela|||0000-0003-3406-6705 Quagliuolo, Vittorio Martín-Broto, Javier|||0000-0001-7350-6916 López Pousa, Antonio Grignani, Giovanni|||0000-0001-5515-569X Blay, Jean-Yves|||0000-0001-7190-120X Diaz Beveridge, Robert Casiraghi, Elena Brich, Silvia|||0000-0002-6359-1712 Renne, Salvatore Lorenzo Bergamaschi, Laura Vergani, Barbara Sbaraglia, Marta Casali, Paolo Giovanni|||0000-0003-4056-8023 Rivoltini, Licia Stacchiotti, Silvia|||0000-0002-1742-8666 Gronchi, Alessandro|||0000-0002-4703-3534 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Anthracycline Neoadjuvant chemotherapy Soft tissue sarcomas Tumour immune microenvironment |
| topic |
Anthracycline Neoadjuvant chemotherapy Soft tissue sarcomas Tumour immune microenvironment |
| description |
Background: Anthracycline-based neoadjuvant chemotherapy (NAC) may modify tumour immune infiltrate. This study characterized immune infiltrate spatial distribution after NAC in primary high-risk soft tissue sarcomas (STS) and investigate association with prognosis. Methods: The ISG-STS 1001 trial randomized STS patients to anthracycline plus ifosfamide (AI) or a histology-tailored (HT) NAC. Four areas of tumour specimens were sampled: the area showing the highest lymphocyte infiltrate (HI) at H&E; the area with lack of post-treatment changes (highest grade, HG); the area with post-treatment changes (lowest grade, LG); and the tumour edge (TE). CD3, CD8, PD-1, CD20, FOXP3, and CD163 were analyzed at immunohistochemistry and digital pathology. A machine learning method was used to generate sarcoma immune index scores (SIS) that predict patient disease-free and overall survival (DFS and OS). Findings: Tumour infiltrating lymphocytes and PD-1+ cells together with CD163+ cells were more represented in STS histologies with complex compared to simple karyotype, while CD20+ B-cells were detected in both these histology groups. PD-1+ cells exerted a negative prognostic value irrespectively of their spatial distribution. Enrichment in CD20+ B-cells at HI and TE areas was associated with better patient outcomes. We generated a prognostic SIS for each tumour area, having the HI-SIS the best performance. Such prognostic value was driven by treatment with AI. Interpretation: The different spatial distribution of immune populations and their different association with prognosis support NAC as a modifier of tumour immune infiltrate in STS. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2 2024-01-01 2024 2024-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/299788 https://dx.doi.org/urn:doi:10.1016/j.ebiom.2024.105220 |
| url |
https://ddd.uab.cat/record/299788 https://dx.doi.org/urn:doi:10.1016/j.ebiom.2024.105220 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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Dipòsit Digital de Documents de la UAB |
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