Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Sci Rep. 2020 Mar 4;10(1):4064. doi: 10.1038/s41598-020-61053-8.
Indications for current immune checkpoint inhibitors are expanding and now include thymic epithelial tumors (TETs). Although clinical trials on immune checkpoint inhibitors for TETs are ongoing, a rationale has not yet been established for immunotherapy for TETs. Therefore, we herein performed phenotypic and functional analyses of T cells in surgically resected TET tissues with a focus on the anti-tumor properties of T cells to TETs as a step towards establishing a rationale for immunotherapy for TETs. We examined T-cell profiles in surgically resected TET tissues, particularly CD4 and CD8 single-positive T cells, using flow cytometry. In the functional analysis of T cells in TETs, we investigated not only cytokine production by T cells, but also their cytotoxicity using bispecific T-cell engager technology. The cluster analysis of T-cell profiles based on flow cytometric data revealed that type B3 thymoma and thymic carcinoma (B3/C) belonged to the hot cluster characterized by a high proportion of Tim-3+ and CD103+ in CD4 and CD8 single-positive T cells. Enhancements in cytokine production and the cytotoxicity of T cells by the anti-PD-1 antibody were significantly greater in B3/C. These results indicate the potential of immunotherapy for patients with B3/C.
目前免疫检查点抑制剂的适应证正在扩大,现在包括胸腺瘤(TET)。尽管针对 TET 的免疫检查点抑制剂的临床试验正在进行中,但针对 TET 的免疫疗法的原理尚未建立。因此,我们在此对手术切除的 TET 组织中的 T 细胞进行了表型和功能分析,重点研究了 T 细胞对 TET 的抗肿瘤特性,以期为 TET 的免疫疗法建立原理。我们使用流式细胞术检查了手术切除的 TET 组织中的 T 细胞谱,特别是 CD4 和 CD8 单阳性 T 细胞。在 TET 中 T 细胞的功能分析中,我们不仅研究了 T 细胞的细胞因子产生,还使用双特异性 T 细胞衔接器技术研究了其细胞毒性。基于流式细胞术数据的 T 细胞谱聚类分析显示,B3 胸腺瘤和胸腺癌(B3/C)属于以 CD4 和 CD8 单阳性 T 细胞中高比例 Tim-3+和 CD103+为特征的热群。抗 PD-1 抗体显著增强了 B3/C 中细胞因子的产生和 T 细胞的细胞毒性。这些结果表明免疫疗法对 B3/C 患者具有潜在的应用价值。