Spatial distribution of tumour immune infiltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy
Pasquali, Sandro (Fondazione IRCCS Istituto Nazionale dei Tumori)
Vallacchi, Viviana (Fondazione IRCCS Istituto Nazionale dei Tumori)
Lalli, Luca (Fondazione IRCCS Istituto Nazionale dei Tumori)
Collini, Paola (Fondazione IRCCS Istituto Nazionale dei Tumori)
Barisella, Marta (ASST Fatebenefratelli Sacco (Itàlia))
Romagosa, Cleofé (Hospital Universitari Vall d'Hebron)
Bagué Rosell, Sílvia (Institut de Recerca Sant Pau)
Coindre, Jean Michel (Institut Bergonié (França))
Dei Tos, Angelo (University of Padua (Itàlia))
Palmerini, Emanuela (IRCCS Istituto Ortopedico Rizzoli (Itàlia))
Quagliuolo, Vittorio (IRCCS Humanitas Research Hospital (Itàlia))
Martín-Broto, Javier (Hospital Universitario Fundación Jiménez Díaz)
López Pousa, Antonio (Institut de Recerca Sant Pau)
Grignani, Giovanni (Città della Salute e della Scienza Hospital (Turin, Itàlia))
Blay, Jean-Yves (Centre Léon Bérard (França))
Diaz Beveridge, Robert (Hospital Universitari i Politècnic La Fe (València))
Casiraghi, Elena (Università degli Studi di Milano (Itàlia))
Brich, Silvia (Fondazione IRCCS Istituto Nazionale dei Tumori)
Renne, Salvatore Lorenzo (Humanitas University (Itàlia))
Bergamaschi, Laura (Fondazione IRCCS Istituto Nazionale dei Tumori)
Vergani, Barbara (University of Milano Bicocca (Itàlia))
Sbaraglia, Marta (University of Padua (Itàlia))
Casali, Paolo Giovanni (Fondazione IRCCS Istituto Nazionale dei Tumori)
Rivoltini, Licia (Fondazione IRCCS Istituto Nazionale dei Tumori)
Stacchiotti, Silvia (Fondazione IRCCS Istituto Nazionale dei Tumori)
Gronchi, Alessandro (Fondazione IRCCS Istituto Nazionale dei Tumori)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	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.
Nota:	Altres ajuts: This work was supported by grants from Pharmamar to Italian Sarcoma Group [grant number not available to A.G.]; grants from the Italian Ministry of Health [RF-2019-12370923 to A.G.; GR-2016-02362609 to V.V.]; 5 x1000 Funds\u20142016, Italian Ministry of Health\u2013Institutional grant BRI2017 from Fondazione IRCCS, Istituto Nazionale dei Tumori di Milano \u201CIntegration of radiOMics, genomICS and immunoprofiling into predictive and prognostic models in soft tissue SARComa patients (SARCOMICS study)\u201D; and AIRC Individual Grant - Next Gen Clinician Scientist [ID#28546 to S.P.].
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Anthracycline ; Neoadjuvant chemotherapy ; Soft tissue sarcomas ; Tumour immune microenvironment
Publicat a:	EBioMedicine, Vol. 106 (august 2024) , p. 105220, ISSN 2352-3964

DOI: 10.1016/j.ebiom.2024.105220
PMID: 39018755

12 p, 2.1 MB

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