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首页> 外文期刊>Cellular immunology >Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and inhibitory receptors
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Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and inhibitory receptors

机译：PD-1和抑制性受体的上调描绘了肿瘤浸润性调节性T细胞

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Foxp3 + regulatory T (T reg) cells are dominant suppressor cells which regulate conventional T (T conv) cells. Inside tumor microenvironment, T reg cells have been known to become potent in suppressing T conv cell responses, thereby enabling tumor cells to circumvent immune response. However, the underlying mechanism by which tumor-infiltrating T reg cells display enhanced suppressive function is still unresolved. To understand characteristics and function of tumor-infiltrating T reg cells as well as T conv cells in the tumor site, we analyzed their phenotypes either within tumor burden or at distant site of tumor using both heterotopic and orthotopic mouse cancer models. Compared to CD8 + T cells at distant site of tumor, tumor-infiltrating CD8 + T cells dramatically upregulated programmed death 1 (PD-1) and other inhibitory receptors, thereby being more exhausted functionally. Tumor-infiltrating CD4 + T cells also expressed higher level of PD-1 than CD4 + T cells at distant site of tumor but very surprisingly, upregulation of PD-1 occurred in CD4 +Foxp3 + T reg as well as CD4 +Foxp3 - T conv cells. Moreover, tumor infiltrating T reg cells upregulated other inhibitory receptors such as T cell immunoglobulin mucin 3 (TIM-3), cytotoxic T lymphocyte antigen-4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and lymphocyte activation gene-3 (LAG-3). These results suggest that upregulation of PD-1 and other inhibitory receptors on tumor-infiltrating T reg cells is related with their enhanced suppressive function.
机译：Foxp3 +调节性T（T reg）细胞是主要的抑制性细胞，可调节常规T（T conv）细胞。在肿瘤微环境内部，已知T reg细胞在抑制T转化细胞反应方面很有效，从而使肿瘤细胞能够规避免疫反应。但是，肿瘤浸润的T reg细胞显示出增强的抑制功能的潜在机制仍未解决。为了了解肿瘤浸润的T reg细胞以及肿瘤部位中的T转化细胞的特征和功能，我们使用异位和原位小鼠癌症模型分析了它们在肿瘤负荷内或肿瘤远处的表型。与肿瘤远处的CD8 + T细胞相比，浸润肿瘤的CD8 + T细胞显着上调了程序性死亡1（PD-1）和其他抑制性受体，从而在功能上更加疲惫。在肿瘤远处，浸润肿瘤的CD4 + T细胞也表达比PD4 + T细胞更高的PD-1水平，但非常令人惊讶的是，PD-1的上调发生在CD4 + Foxp3 + T reg以及CD4 + Foxp3-T中转化细胞。此外，肿瘤浸润性T reg细胞上调了其他抑制性受体，例如T细胞免疫球蛋白粘蛋白3（TIM-3），细胞毒性T淋巴细胞抗原4（CTLA-4），糖皮质激素诱导的肿瘤坏死因子受体（GITR）和淋巴细胞活化基因3（LAG-3）。这些结果表明，PD-1和其他抑制性受体在肿瘤浸润性T reg细胞上的上调与其抑制功能增强有关。

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