研究动态
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由马列克病毒生成的肿瘤微环境压制γδT细胞产生干扰素-γ。

The tumor microenvironment generated by Marek's disease virus suppresses interferon-gamma-producing gamma delta T cells.

发表日期:2023 Sep 12
作者: Ayumi Matsuyama-Kato, Nitish Boodhoo, Sugandha Raj, Mohamed Faizal Abdul-Careem, Brandon L Plattner, Shahriar Behboudi, Shayan Sharif
来源: VETERINARY MICROBIOLOGY

摘要:

肿瘤微环境(TME)由肿瘤细胞、免疫系统细胞和基质细胞之间的相互作用产生。玛瑞克病病毒(MDV)生成的TME据推测显示出一种免疫抑制性环境,这是由于MDV转化的细胞和调节性T细胞所诱导的免疫抑制性分子和细胞因子。在人类癌症中报告了抗肿瘤和促肿瘤γδT细胞。尽管在MDV感染的鸡的后期阶段发现了与抗肿瘤和促肿瘤γδT细胞类似的细胞,但尚未调查TME如何影响循环和组织驻留的γδT细胞。在这里,我们证明了从MDV挑战的鸡中获得的脾细胞培养上清液抑制了通过T细胞受体(TCR)γδ刺激的组织驻留γδT细胞的干扰素(IFN)-γ产生和CD25表达,但是从MDV转化的细胞系培养上清液对γδT细胞的激活没有影响。通过TCRγδ刺激的循环γδT细胞既不受从MDV挑战的鸡脾细胞培养上清液的影响,也不受从MDV转化的细胞系培养上清液的影响。综上所述,MDV生成的TME可以抑制组织驻留γδT细胞的激活和IFN-γ的产生,而肿瘤吸引的循环γδT细胞可能不受MDV生成的TME对激活和IFN-γ产生的影响。 © 2023版权归Elsevier B.V.所有。
The tumor microenvironment (TME) is generated by the cross-talk among tumor cells, immune system cells, and stromal cells. The TME generated by Marek's disease virus (MDV) is suggested to display an immunosuppressive milieu due to immune inhibitory molecules and cytokines which are possibly induced by MDV-transformed cells and regulatory T cells. Both anti-tumor and pro-tumor gamma delta (γδ) T cells are reported in human cancer. Although anti-tumor like and pro-tumor like γδ T cells are found in MDV-infected chickens at the later phase of infection, how the TME affects circulating and tissue-resident γδ T cells has not been investigated. Here, we demonstrated that the supernatant of the cultured splenocytes derived from MDV-challenegd chickens inhibited interferon (IFN)-γ production and CD25 expression by T cell receptor (TCR)γδ-stimulated tissue-resident γδ T cells, but the supernatant of the cultured MDV-transformed cell line did not affect γδ T cell activation. TCRγδ-stimulated circulating γδ T cells were influenced neither by the supernatant of the cultured splenocytes derived from MDV-challenegd chickens nor by the supernatant of the cultured MDV-transformed cell line. Taken together, activation and IFN-γ production by tissue-resident γδ T cells can be inhibited in the TME generated by MDV while tumor attracted circulating γδ T cells may not be influenced in activation and IFN-γ production by the TME generated by MDV.Copyright © 2023. Published by Elsevier B.V.