Gultekin Okan, Gonzalez-Molina Jordi, Hardell Elin, Moyano-Galceran Lidia, Mitsios Nicholas, Mulder Jan, Kokaraki Georgia, Isaksson Anders, Sarhan Dhifaf, Lehti Kaisa, Carlson Joseph W
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
NPJ Precis Oncol. 2021 Nov 19;5(1):97. doi: 10.1038/s41698-021-00236-6.
Uterine sarcomas are rare but deadly malignancies without effective treatment. Immunotherapy is a promising new approach to treat these tumors but has shown heterogeneous effects in sarcoma patients. With the goal of identifying key factors for improved patient treatment, we characterized the tumor immune landscape in 58 uterine sarcoma cases with full clinicopathological annotation. Immune cell characterization revealed the overall prevalence of FOXP3+ cells and pro-tumor M2-like macrophages. Hierarchical clustering of patients showed four tumor type-independent immune signatures, where infiltration of FOXP3+ cells and M1-like macrophages associated with favorable prognosis. High CD8+/FOXP3+ ratio in UUS and ESS correlated with poor survival, upregulation of immunosuppressive markers, extracellular matrix (ECM)-related genes and proteins, and YAP activation. This study shows that uterine sarcomas present distinct immune signatures with prognostic value, independent of tumor type, and suggests that targeting the ECM could be beneficial for future treatments.
子宫肉瘤虽罕见但却是致命的恶性肿瘤，且尚无有效治疗方法。免疫疗法是治疗这些肿瘤的一种有前景的新方法，但在肉瘤患者中显示出异质性效果。为了确定改善患者治疗的关键因素，我们对58例具有完整临床病理注释的子宫肉瘤病例的肿瘤免疫格局进行了表征。免疫细胞表征揭示了FOXP3 +细胞和促肿瘤M2样巨噬细胞的总体流行情况。患者的层次聚类显示出四种与肿瘤类型无关的免疫特征，其中FOXP3 +细胞和M1样巨噬细胞的浸润与良好预后相关。子宫平滑肌肉瘤（UUS）和子宫内膜间质肉瘤（ESS）中高CD8 + / FOXP3 +比率与较差的生存率、免疫抑制标志物、细胞外基质（ECM）相关基因和蛋白质的上调以及YAP激活有关。这项研究表明，子宫肉瘤呈现出具有预后价值的独特免疫特征，与肿瘤类型无关，并表明靶向ECM可能对未来治疗有益。
