Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors
Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors
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DOI：
10.1038/s41598-020-61053-8
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发表时间：
2020-03-04
影响因子：
4.6
通讯作者：
Wada, Hisashi
中科院分区：
文献类型：
--
作者：
Yamamoto, Yoko;Iwahori, Kota;Wada, Hisashi
目前免疫检查点抑制剂的适应症正在扩大，现在包括胸腺上皮肿瘤(TETS)。尽管针对TETS的免疫检查点抑制剂的临床试验仍在进行中，但针对TETS的免疫治疗的理论基础尚未建立。因此，我们在这里对手术切除的TET组织中的T细胞进行了表型和功能分析，重点是T细胞对TETS的抗肿瘤特性，作为建立TETS免疫治疗的理论基础的一步。我们用流式细胞术检测了手术切除的TET组织中的T细胞图谱，特别是CD4和CD8单阳性T细胞。在TETS中T细胞的功能分析中，我们不仅研究了T细胞产生的细胞因子，而且利用双特异性T细胞结合技术研究了它们的细胞毒作用。基于流式细胞仪数据的T细胞谱聚类分析显示，B3型胸腺瘤和胸腺癌(B3/C)属于热点聚集区，其特点是在CD4和CD8单阳性T细胞中Tim-3+和CD103+比例较高。在B3/C中，抗PD-1抗体对细胞因子的产生和T细胞的细胞毒作用的促进作用明显更强。这些结果表明B3/C患者免疫治疗的潜力。
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.