Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy.
Translational Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy.
EBioMedicine. 2024 Aug;106:105220. doi: 10.1016/j.ebiom.2024.105220. Epub 2024 Jul 16.
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.
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).
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.
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].
蒽环类药物为基础的新辅助化疗（NAC）可能会改变肿瘤免疫浸润。本研究对原发性高危软组织肉瘤（STS）NAC 后肿瘤免疫浸润的空间分布进行了特征描述，并探讨了其与预后的关系。
ISG-STS1001 试验将 STS 患者随机分为蒽环类药物加异环磷酰胺（AI）或基于组织学的（HT）NAC 组。对肿瘤标本的四个区域进行取样：H&E 显示淋巴细胞浸润最高的区域（HI）；治疗后无变化的区域（最高分级，HG）；治疗后有变化的区域（最低分级，LG）；以及肿瘤边缘（TE）。采用免疫组织化学和数字病理学分析 CD3、CD8、PD-1、CD20、FOXP3 和 CD163。使用机器学习方法生成预测患者无病和总生存（DFS 和 OS）的肉瘤免疫指数评分（SIS）。
与简单核型相比，具有复杂核型的 STS 组织学中浸润的淋巴细胞和 PD-1+细胞以及 CD163+细胞更多，而 CD20+B 细胞在这两种组织学类型中均有检测到。PD-1+细胞的空间分布对预后有负面影响。HI 和 TE 区域 CD20+B 细胞的富集与患者预后较好相关。我们为每个肿瘤区域生成了一个预后 SIS，其中 HI-SIS 表现最好。这种预后价值是由 AI 治疗驱动的。
不同免疫细胞群的空间分布及其与预后的不同关联支持 NAC 作为 STS 肿瘤免疫浸润的修饰剂。
Pharmamar；意大利卫生部[RF-2019-12370923；GR-2016-02362609]；2016 年 5×1000 基金，意大利卫生部；AIRC 资助[ID#28546]。
