Spatial distribution of tumour immune in fi ltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy
Por:
Pasquali, S, Vallacchi, V, Lalli, L, Collini, P, Barisella, M, Romagosa, C, Bague, S, Coindre, JM, Dei Tos, AP, Palmerini, E, Quagliuolo, V, Martin-Broto, J, Lopez-Pousa, A, Grignani, G, Blay, JY, Beveridge, RD, Casiraghi, E, Brich, S, Renne, SL, Bergamaschi, L, Vergani, B, Sbaraglia, M, Casali, PG, Rivoltini, L, Stacchiotti, S, Gronchi, A
Publicada:
1 ago 2024
Ahead of Print:
1 jul 2024
Resumen:
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.
Filiaciones:
Pasquali, S:
Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, Mol Pharmacol, Via GAmadeo 42, I-20133 Milan, Italy
Vallacchi, V:
Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, Translat Immunol Unit, Via G Venezian 1, I-20133 Milan, Italy
Lalli, L:
Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, Translat Immunol Unit, Via G Venezian 1, I-20133 Milan, Italy
Collini, P:
Fdn IRCCS Ist Nazl Tumori Milano, Dept Adv Diagnost, Soft Tissue Tumor Pathol Unit, Milan, Italy
Barisella, M:
ASST Fatebenefratelli Sacco, Pathol Unit, Milan, Italy
Romagosa, C:
Vall dHebron Univ Hosp, Pathol Dept, Barcelona, Spain
Bague, S:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Pathol Dept, Barcelona, Spain
Coindre, JM:
Inst Bergonie, Dept Pathol, F-33000 Bordeaux, France
Inst Bergonie, INSERM U1218 ACTION, F-33000 Bordeaux, France
Dei Tos, AP:
Univ Padua, Dept Med DIMED, Surg Pathol & Cytopathol Unit, Padua, Italy
Palmerini, E:
IRCCS Ist Ortoped Rizzoli, Osteoncol Bone & Soft Tissue Sarcomas & Innovat Th, Bologna, Italy
Quagliuolo, V:
IRCCS Humanitas Res Hosp, Surg Dept, Rozzano, Italy
Martin-Broto, J:
Fdn Jimenez Diaz Univ Hosp, Oncol Dept, Madrid, Spain
Lopez-Pousa, A:
Hosp Santa Creu & Sant Pau, Med Oncol Dept, Carrer St Quinti 89, Barcelona 08041, Spain
Grignani, G:
Citta Salute & Sci Hosp, Med Oncol Unit, Turin, Italy
Blay, JY:
Ctr Leon Berard, Lyon, France
Univ Claude Bernard Lyon 1, Lyon, France
Beveridge, RD:
Hosp Univ & Politecn La Fe, Dept Canc Med, Valencia, Spain
Casiraghi, E:
Univ Milan, Dept Comp Sci Giovanni Degli Antoni, AnacletoLab, Milan, Italy
Brich, S:
Fdn IRCCS Ist Nazl Tumori Milano, Dept Adv Diagnost, Soft Tissue Tumor Pathol Unit, Milan, Italy
Renne, SL:
IRCCS Humanitas Res Hosp, Pathol Dept, Rozzano, Italy
Humanitas Univ, Dept Biomed Sci, Pieve Emanuele, Milan, Italy
Bergamaschi, L:
Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, Translat Immunol Unit, Via G Venezian 1, I-20133 Milan, Italy
Vergani, B:
Univ Milano Bicocca, Sch Med & Surg, Monza, Italy
Sbaraglia, M:
Univ Padua, Dept Med DIMED, Surg Pathol & Cytopathol Unit, Padua, Italy
Casali, PG:
Fdn IRCCS Ist Nazl Tumori Milano, Dept Canc Med, Milan, Italy
Rivoltini, L:
Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, Translat Immunol Unit, Via G Venezian 1, I-20133 Milan, Italy
Stacchiotti, S:
Fdn IRCCS Ist Nazl Tumori Milano, Dept Canc Med, Milan, Italy
Gronchi, A:
Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Serv, Via G Venezian 1, I-20133 Milan, Italy
Green Published, gold
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