Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.
Department of Pediatrics, University of Colorado, Aurora, CO, USA.
Cancer Immunol Immunother. 2021 Dec;70(12):3489-3499. doi: 10.1007/s00262-021-02928-1. Epub 2021 Apr 24.
The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.
脂肪肉瘤的肿瘤免疫微环境特征尚不清楚,本研究旨在确定肿瘤免疫微环境对不同脂肪肉瘤亚型的预后影响。共纳入 70 例脂肪肉瘤患者,包括黏液样脂肪肉瘤(n=45)、去分化脂肪肉瘤(n=17)和多形性脂肪肉瘤(n=8)。通过免疫组织化学检测肿瘤浸润淋巴细胞(CD4+、CD8+、FOXP3+淋巴细胞)和 CD163+巨噬细胞的存在,以及 HLA Ⅰ类和 PD-L1 的表达,从结局数据中评估总生存和无进展生存。与黏液样脂肪肉瘤患者相比,去分化脂肪肉瘤和多形性脂肪肉瘤患者的浸润淋巴细胞和巨噬细胞数量明显更多。而高巨噬细胞数的黏液样脂肪肉瘤患者总生存和无进展生存更差,高巨噬细胞数的去分化脂肪肉瘤患者则有更好的预后趋势。45 例黏液样脂肪肉瘤中有 35 例(77.8%)HLA Ⅰ类表达阴性,而所有去分化脂肪肉瘤和多形性脂肪肉瘤均表达 HLA Ⅰ类。高 HLA Ⅰ类表达的黏液样脂肪肉瘤患者总生存和无进展生存明显较差,而高 HLA Ⅰ类表达的去分化脂肪肉瘤患者则有较好的结局。17 例去分化脂肪肉瘤中有 4 例(23.5%)、8 例多形性脂肪肉瘤中有 2 例(25%)和无黏液样脂肪肉瘤表达 PD-L1。我们的结果表明,与其他脂肪肉瘤亚型相比,黏液样脂肪肉瘤具有独特的免疫微环境,提示脂肪肉瘤的免疫治疗方法应基于亚型。