单相和双相滑膜肉瘤的免疫差异及其对免疫治疗的意义。
Immunological differences between monophasic and biphasic synovial sarcoma with implications for immunotherapy.
作者信息
Luk S J, IJsselsteijn M E, Somarakis A, Acem I, de Bruijn I Briaire, Szuhai K, Bovee J V M G, de Miranda N F C C, Falkenburg J H F, Heemskerk M H M
机构信息
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
出版信息
Cancer Immunol Immunother. 2024 Dec 21;74(1):31. doi: 10.1007/s00262-024-03868-2.
Synovial sarcoma is an aggressive soft-tissue cancer that shows limited responses to current immunotherapeutic approaches using immune checkpoint blockade or adoptive cell therapy. To improve immunotherapy for this cancer, understanding how the immune cells in the tumor microenvironment associate with histological subtype, disease progression and current therapies is vital. To evaluate the immune infiltrate in synovial sarcoma in relation to histological subtype, disease progression and in response to cytotoxic treatment, we performed immunodetection of T cells, CD68 myeloid cells, endothelial cells and keratin on a series of 41 synovial sarcoma patients at various stages of disease. The immune composition of synovial sarcoma was dominated by CD68 myeloid cells of which a substantial part was of the CD163 immunosuppressive phenotype, which increased after chemotherapy or radiotherapy. Biphasic synovial sarcomas were more densely infiltrated by both T cells and myeloid cells than monophasic synovial sarcomas. In these tumors, the immune and endothelial cells were mostly located within the stromal like, spindle cell compartment and excluded from the epithelial compartment, greatly resembling the spatial organization of healthy epithelium such as in the colon. Together these data demonstrate that biphasic synovial sarcoma is immunologically different from monophasic synovial sarcoma and might be more susceptible to immunotherapies such as adoptive T-cell therapy. Finally, T-cell infiltration in primary synovial sarcoma was associated with prolonged overall survival of patients which suggests that intratumoral T cells may demonstrate anti-tumor activity.
滑膜肉瘤是一种侵袭性软组织癌,对目前使用免疫检查点阻断或过继性细胞疗法的免疫治疗方法反应有限。为了改善这种癌症的免疫治疗,了解肿瘤微环境中的免疫细胞如何与组织学亚型、疾病进展及当前治疗相关至关重要。为了评估滑膜肉瘤中与组织学亚型、疾病进展及对细胞毒性治疗反应相关的免疫浸润情况,我们对41例处于疾病不同阶段的滑膜肉瘤患者进行了一系列检测,对T细胞、CD68髓样细胞、内皮细胞和角蛋白进行免疫检测。滑膜肉瘤的免疫组成以CD68髓样细胞为主,其中很大一部分是CD163免疫抑制表型,在化疗或放疗后增加。双相滑膜肉瘤比单相滑膜肉瘤的T细胞和髓样细胞浸润更密集。在这些肿瘤中,免疫细胞和内皮细胞大多位于基质样梭形细胞区,而在上皮区则没有,这与健康上皮(如结肠上皮)的空间组织非常相似。这些数据共同表明,双相滑膜肉瘤在免疫方面与单相滑膜肉瘤不同,可能对过继性T细胞疗法等免疫治疗更敏感。最后,原发性滑膜肉瘤中的T细胞浸润与患者的总生存期延长相关,这表明肿瘤内T细胞可能具有抗肿瘤活性。
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