Spatial distribution of tumour immune in fi ltrate predicts outcomes of patients with high-risk soft tissue sarcomas after neoadjuvant chemotherapy

被引：2

作者：

Pasquali, Sandro ^{[1
]}

Vallacchi, Viviana ^{[2
]}

Lalli, Luca ^{[2
]}

Collini, Paola ^{[3
]}

Barisella, Marta ^{[4
]}

Romagosa, Cleofe ^{[5
]}

Bague, Silvia ^{[6
]}

Coindre, Jean Michel ^{[7
,8
]}

Dei Tos, Angelo Paolo ^{[9
]}

Palmerini, Emanuela ^{[10
]}

Quagliuolo, Vittorio ^{[11
]}

Martin-Broto, Javier ^{[12
]}

Lopez-Pousa, Antonio ^{[13
]}

Grignani, Giovanni ^{[14
]}

Blay, Jean-Yves ^{[15
,16
]}

Beveridge, Robert Diaz ^{[17
]}

Casiraghi, Elena ^{[18
]}

Brich, Silvia ^{[3
]}

Renne, Salvatore Lorenzo ^{[19
,20
]}

Bergamaschi, Laura ^{[2
]}

Vergani, Barbara ^{[21
]}

Sbaraglia, Marta ^{[9
]}

Casali, Paolo Giovanni ^{[22
]}

Rivoltini, Licia ^{[2
]}

Stacchiotti, Silvia ^{[22
]}

Gronchi, Alessandro ^{[23
]}

机构：

[1] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, Mol Pharmacol, Via GAmadeo 42, I-20133 Milan, Italy

[2] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, Translat Immunol Unit, Via G Venezian 1, I-20133 Milan, Italy

[3] Fdn IRCCS Ist Nazl Tumori Milano, Dept Adv Diagnost, Soft Tissue Tumor Pathol Unit, Milan, Italy

[4] ASST Fatebenefratelli Sacco, Pathol Unit, Milan, Italy

[5] Vall dHebron Univ Hosp, Pathol Dept, Barcelona, Spain

[6] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Pathol Dept, Barcelona, Spain

[7] Inst Bergonie, Dept Pathol, F-33000 Bordeaux, France

[8] Inst Bergonie, INSERM U1218 ACTION, F-33000 Bordeaux, France

[9] Univ Padua, Dept Med DIMED, Surg Pathol & Cytopathol Unit, Padua, Italy

[10] IRCCS Ist Ortoped Rizzoli, Osteoncol Bone & Soft Tissue Sarcomas & Innovat Th, Bologna, Italy

[11] IRCCS Humanitas Res Hosp, Surg Dept, Rozzano, Italy

[12] Fdn Jimenez Diaz Univ Hosp, Oncol Dept, Madrid, Spain

[13] Hosp Santa Creu & Sant Pau, Med Oncol Dept, Carrer St Quinti 89, Barcelona 08041, Spain

[14] Citta Salute & Sci Hosp, Med Oncol Unit, Turin, Italy

[15] Ctr Leon Berard, Lyon, France

[16] Univ Claude Bernard Lyon 1, Lyon, France

[17] Hosp Univ & Politecn La Fe, Dept Canc Med, Valencia, Spain

[18] Univ Milan, Dept Comp Sci Giovanni Degli Antoni, AnacletoLab, Milan, Italy

[19] IRCCS Humanitas Res Hosp, Pathol Dept, Rozzano, Italy

[20] Humanitas Univ, Dept Biomed Sci, Pieve Emanuele, Milan, Italy

[21] Univ Milano Bicocca, Sch Med & Surg, Monza, Italy

[22] Fdn IRCCS Ist Nazl Tumori Milano, Dept Canc Med, Milan, Italy

[23] Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Serv, Via G Venezian 1, I-20133 Milan, Italy

来源：

EBIOMEDICINE | 2024年 / 106卷

关键词：

Soft tissue sarcomas; Tumour immune microenvironment; Neoadjuvant chemotherapy; Anthracycline; B-CELLS; OPEN-LABEL; PEMBROLIZUMAB; DOXORUBICIN; SURVIVAL; MULTICENTER; NIVOLUMAB; EFFICACY;

D O I：

10.1016/j.ebiom.2024.105220

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：12

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