Spatial distribution of tumour immune in fi ltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy
Background Anthracycline-based neoadjuvant chemotherapy (NAC) may modify tumour immune in fi ltrate. This study characterized immune in fi ltrate spatial distribution after NAC in primary high-risk soft tissue sarcomas (STS) and investigate association with prognosis. Methods The ISG-STS 1001 trial...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p18114 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=18114 http://ddd.uab.cat/record/299788 |
| Access Level: | acceso abierto |
| Palabra clave: | Soft tissue sarcomas Tumour immune microenvironment Neoadjuvant chemotherapy Anthracycline |
| Sumario: | Background Anthracycline-based neoadjuvant chemotherapy (NAC) may modify tumour immune in fi ltrate. This study characterized immune in fi ltrate 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 in fi ltrate (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 in fi ltrating 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 modi fi er of tumour immune in fi ltrate in STS. |
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