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...

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Detalhes bibliográficos
Autores: 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
Tipo de documento: artigo
Data de publicação:2024
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:299788
Acesso em linha:https://ddd.uab.cat/record/299788
https://dx.doi.org/urn:doi:10.1016/j.ebiom.2024.105220
Access Level:Acceso aberto
Palavra-chave:Anthracycline
Neoadjuvant chemotherapy
Soft tissue sarcomas
Tumour immune microenvironment
Descrição
Resumo: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.

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