Department of Pathology, University of Virginia, Charlottesville, VA.
Am J Surg Pathol. 2019 Jun;43(6):792-801. doi: 10.1097/PAS.0000000000001254.
Immunotherapies targeting the PD-1/PD-L1 checkpoint axis are of growing interest for the treatment of mesenchymal neoplasms. However, PD-L1 expression and tumor-associated lymphocytes have not been well-investigated in uterine smooth muscle tumors. Forty-nine uterine smooth muscle tumors (23 leiomyosarcomas, 8 smooth muscle tumors of uncertain malignant potential [STUMP], 7 atypical leiomyomas, and 11 benign leiomyomas) were evaluated for tumoral and tumor-associated immune PD-L1 expression and tumor-associated T-cell infiltration. ALK immunohistochemistry was performed to exclude inflammatory myofibroblastic tumors. Tumor PD-L1 expression was seen in 70% of leiomyosarcomas and 14% of atypical leiomyomas; no cases of STUMP or benign leiomyoma demonstrated tumoral PD-L1. PD-L1 positivity was seen in tumor-associated immune cells in 78% of leiomyosarcomas, 25% of STUMP, no cases of atypical leiomyomas, and 9% of benign leiomyomas. Of the 23 leiomyosarcomas, 15 (65%) had a combined positive score ≥1, while of the 26 other uterine smooth muscle tumors, only 2 (8%) had a combined positive score ≥1. Tumor-associated CD8+ cells were highest among leiomyosarcomas (mean: 87/high-power fields vs. 17/high-power fields for nonleiomyosarcomas), and were significantly associated with PD-L1 expression. One PD-L1, CD8-enriched leiomyosarcoma showed an ALK overexpression suggesting possible classification as inflammatory myofibroblastic tumor, but otherwise lacked morphologic features of this entity. Leiomyosarcomas demonstrate significantly higher PD-L1 expression and cytotoxic T-cell infiltration when compared with other uterine smooth muscle tumors. These data suggest the possibility that treatment with targeted immunotherapy may be appropriate in a selected population of patients with leiomyosarcoma and, potentially, in related tumors bearing ALK rearrangements.
针对 PD-1/PD-L1 检查点轴的免疫疗法越来越受到人们的关注，用于治疗间叶性肿瘤。然而，PD-L1 表达和肿瘤相关淋巴细胞在子宫平滑肌肿瘤中尚未得到充分研究。评估了 49 例子宫平滑肌肿瘤（23 例平滑肌肉瘤、8 例平滑肌肿瘤恶性潜能不确定[STUMP]、7 例非典型平滑肌瘤和 11 例良性平滑肌瘤）的肿瘤相关免疫 PD-L1 表达和肿瘤相关 T 细胞浸润情况。进行了 ALK 免疫组化检查以排除炎性肌纤维母细胞瘤。70%的平滑肌肉瘤和 14%的非典型平滑肌瘤存在肿瘤 PD-L1 表达；无 STUMP 或良性平滑肌瘤存在肿瘤 PD-L1。在 78%的平滑肌肉瘤、25%的 STUMP、无非典型平滑肌瘤和 9%的良性平滑肌瘤中观察到肿瘤相关免疫细胞中的 PD-L1 阳性。23 例平滑肌肉瘤中有 15 例（65%）的联合阳性评分≥1，而在其他 26 例子宫平滑肌肿瘤中，仅有 2 例（8%）的联合阳性评分≥1。肿瘤相关 CD8+细胞在平滑肌肉瘤中最高（平均值：87/高倍视野与非平滑肌肉瘤的 17/高倍视野），与 PD-L1 表达显著相关。1 例 PD-L1、CD8 富集的平滑肌肉瘤表现出 ALK 过表达，提示可能分类为炎性肌纤维母细胞瘤，但在其他方面缺乏该实体的形态特征。与其他子宫平滑肌肿瘤相比，平滑肌肉瘤显示出更高的 PD-L1 表达和细胞毒性 T 细胞浸润。这些数据表明，在选择的平滑肌肉瘤患者和可能具有 ALK 重排的相关肿瘤患者中，靶向免疫治疗可能是合适的。
