Sistema de Salut de Catalunya
Institut Català de la Salut
[Pasquali S] Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy. [Vallacchi V, Lalli L] Translational Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy. [Collini P] Soft Tissue Tumor Pathology Unit, Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy. [Barisella M] Pathology Unit, ASST Fatebenefratelli Sacco, Milan, Italy. [Romagosa C] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2024-07-31T08:20:05Z
2024-07-31T08:20:05Z
2024-07-16
Anthracycline; Neoadjuvant chemotherapy; Soft tissue sarcomas
Antraciclina; Quimioterapia neoadyuvante; Sarcomas de tejidos blandos
Antraciclina; Quimioteràpia neoadjuvant; Sarcomes de teixits tous
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.
Pharmamar; Italian Ministry of Health [RF-2019-12370923; GR-2016-02362609]; 5 × 1000 Funds—2016, Italian Ministry of Health; AIRC Grant [ID#28546].
Article
Published version
English
Sarcoma - Tractament; Tumors de parts toves - Tractament; Limfòcits; Avaluació de resultats (Assistència sanitària); DISEASES::Neoplasms::Neoplasms by Site::Soft Tissue Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy; DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Sarcoma; ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocytes, Tumor-Infiltrating; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de los tejidos blandos; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::tratamiento neoadyuvante; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::sarcoma; ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos infiltrantes de tumor; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
Elsevier
eBioMedicine;106
https://doi.org/10.1016/j.ebiom.2024.105220
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
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