研究动态
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Tespa1缺乏在小鼠Lewis肺癌模型中通过减少CD8+T细胞活性降低了抗肿瘤免疫反应。

Tespa1 deficiency reduces the antitumour immune response by decreasing CD8+T cell activity in a mouse Lewis lung cancer model.

发表日期:2023 Sep 01
作者: Ruhui Yang, Mingyue Yang, Zehua Wu, Bingjin Liu, Mingzhu Zheng, Linrong Lu, Songquan Wu
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

Thymocyte-expressed, positive selection-associated 1 (Tespa1)是T细胞发育的关键分子,与免疫相关疾病有关。然而,它在抗肿瘤CD8+T细胞免疫中的作用尚不清楚。在这里,我们证明了Tespa1在抗肿瘤CD8+T细胞免疫中起着重要作用。首先,与野生型(WT)小鼠相比,Tespa1基因敲除(Tespa1-/-)小鼠中的Lewis肺癌细胞生长更快,凋亡减少,并且外周血和肿瘤组织中的CD8+T细胞减少。其次,Tespa1-/-小鼠的脾细胞中CD8+T细胞和Th1细胞的比例低于WT小鼠。第三,Tespa1-/- CD8+肿瘤浸润淋巴细胞(TILs)的增殖、侵袭、细胞毒性和IL-2信号通路成分的蛋白表达相比WT CD8+TILs都较弱。此外,Tespa1-/-小鼠中CD8+TILs的PD-1表达高于WT小鼠。最后,WT小鼠的CD8+TILs改善了Tespa1-/-小鼠的抗肿瘤能力。总之,这些发现表明Tespa1通过调节CD8+T细胞在肿瘤免疫系统中起着关键作用。版权所有 © 2023 Elsevier B.V. 保留所有权利。
Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a key molecule in T-cell development and has been linked to immune diseases. However, its role in antitumour CD8+T cell immunity remains unclear. Here, we demonstrated that Tespa1 plays an important role in antitumour CD8+T cell immunity. First, compared with wild-type (WT) mice, Lewis lung cancer cells grew faster in Tespa1 knockout (Tespa1-/-) mice, with reduced apoptosis, and decreased CD8+T cells in peripheral blood and tumor tissues. Second, the proportion of CD8+T and Th1 cells in the splenocytes of Tespa1-/- mice was lower than that in WT mice. Third, Tespa1-/- CD8+ tumor-infiltrating lymphocytes (TILs) showed weakened proliferation, invasion, cytotoxicity, and protein expression of IL-2 signalling pathway components compared to WT CD8+TILs. Furthermore, PD-1 expression in CD8+TILs was higher in Tespa1-/- than in WT mice. Lastly, CD8+TILs in WT mice improved the antitumour ability of Tespa1-/- mice. In conclusion, these findings suggest that Tespa1 plays a critical role in the tumor immune system by regulating CD8+T cells.Copyright © 2023 Elsevier B.V. All rights reserved.