Department of Orthopaedics and Trauma, Medical University of Graz, Graz, Austria.
Center for Biomarker Research in Medicine (CBmed), Graz, Austria.
Oncoimmunology. 2021 Mar 11;10(1):1896658. doi: 10.1080/2162402X.2021.1896658.
Soft tissue sarcomas (STS) are considered non-immunogenic, although distinct entities respond to anti-tumor agents targeting the tumor microenvironment. This study's aims were to investigate relationships between tumor-infiltrating immune cells and patient/tumor-related factors, and assess their prognostic value for local recurrence (LR), distant metastasis (DM), and overall survival (OS). One-hundred-eighty-eight STS-patients (87 females [46.3%]; median age: 62.5 years) were retrospectively analyzed. Tissue microarrays (in total 1266 cores) were stained with multiplex immunohistochemistry and analyzed with multispectral imaging. Seven cell types were differentiated depending on marker profiles (CD3+, CD3+ CD4+ helper, CD3+ CD8+ cytotoxic, CD3+ CD4+ CD45RO+ helper memory, CD3+ CD8+ CD45RO+ cytotoxic memory T-cells; CD20 + B-cells; CD68+ macrophages). Correlations between phenotype abundance and variables were analyzed. Uni- and multivariate Fine&Gray and Cox-regression models were constructed to investigate prognostic variables. Model calibration was assessed with C-index. IHC-findings were validated with TCGA-SARC gene expression data of genes specific for macrophages, T- and B-cells. B-cell percentage was lower in patients older than 62.5 years ( = .013), whilst macrophage percentage was higher ( = .002). High B-cell ( = .035) and macrophage levels ( = .003) were associated with increased LR-risk in the univariate analysis. In the multivariate setting, high macrophage levels ( = .014) were associated with increased LR-risk, irrespective of margins, age, gender or B-cells. Other immune cells were not associated with outcome events. High macrophage levels were a poor prognostic factor for LR, irrespective of margins, B-cells, gender and age. Thus, anti-tumor, macrophage-targeting agents may be applied more frequently in tumors with enhanced macrophage infiltration.
软组织肉瘤（STS）被认为是非免疫原性的，尽管不同的实体对靶向肿瘤微环境的抗肿瘤药物有反应。本研究旨在探讨肿瘤浸润免疫细胞与患者/肿瘤相关因素之间的关系，并评估其对局部复发（LR）、远处转移（DM）和总生存（OS）的预后价值。对 188 名 STS 患者（87 名女性[46.3%]；中位年龄：62.5 岁）进行回顾性分析。组织微阵列（共 1266 个核心）用多重免疫组化染色，并用多光谱成像分析。根据标志物谱将七种细胞类型区分开来（CD3+、CD3+CD4+辅助细胞、CD3+CD8+细胞毒性细胞、CD3+CD4+CD45RO+辅助记忆细胞、CD3+CD8+CD45RO+细胞毒性记忆 T 细胞；CD20+B 细胞；CD68+巨噬细胞）。分析表型丰度与变量之间的相关性。构建单变量和多变量 Fine&Gray 和 Cox 回归模型，以研究预后变量。用 C 指数评估模型校准。用 TCGA-SARC 基因表达数据验证免疫组化结果，该数据是特定于巨噬细胞、T 细胞和 B 细胞的基因。年龄大于 62.5 岁的患者中 B 细胞比例较低（=.013），而巨噬细胞比例较高（=.002）。在单变量分析中，高 B 细胞（=.035）和巨噬细胞水平（=.003）与 LR 风险增加相关。在多变量分析中，高巨噬细胞水平（=.014）与 LR 风险增加相关，与切缘、年龄、性别或 B 细胞无关。其他免疫细胞与结局事件无关。高巨噬细胞水平是 LR 的不良预后因素，与切缘、B 细胞、性别和年龄无关。因此，针对肿瘤的、针对巨噬细胞的靶向药物可能会更频繁地应用于浸润巨噬细胞增强的肿瘤。
