文章目录

CD8+ t细胞分泌的IFN-γ对旁观者肿瘤细胞的远距离调节

原文发布日期：2020-03-09

英文摘要：

摘要翻译：

原文链接：

文章：

CD8+ t细胞分泌的IFN-γ对旁观者肿瘤细胞的远距离调节

Long-distance modulation of bystander tumor cells by CD8+ T-cell-secreted IFN-γ

原文发布日期：2020-03-09

英文摘要：

T-cell-secreted interferon (IFN)-γ can exert pleiotropic effects on tumor cells that include induction of immune checkpoints and antigen presentation machinery components, and inhibition of cell growth. Despite its role as a key effector molecule, little is known about the spatiotemporal spreading of IFN-γ secreted by activated CD8+ T cells within the tumor environment. Using multiday intravital imaging, we demonstrate that T cell recognition of a minor fraction of tumor cells leads to sensing of IFN-γ by a large part of the tumor mass. Furthermore, imaging of tumors in which antigen-positive and antigen-negative tumor cells are separated in space reveals spreading of the IFN-γ response, reaching distances of >800 µm. Notably, long-range sensing of IFN-γ can modify tumor behavior, as shown by both induction of PD-L1 expression and inhibition of tumor growth. Collectively, these data reveal how, through IFN-γ, CD8+ T cells modulate the behavior of remote tumor cells, including antigen-loss variants.

摘要翻译：

T 细胞分泌的干扰素 γ（IFN-γ）对肿瘤细胞的影响不仅限于诱导免疫 Checkpoints 和抗原呈递机制组件，还可能抑制细胞生长。尽管作为关键执行分子之一，对其在肿瘤环境中由活化的 CD8+ T 细胞释放的 IFN-γ的空间时间扩散尚知甚少。通过多日体内切实验，我们发现，T 细胞识别了一部分肿瘤细胞，导致大部分肿瘤组织感知了 IFN-γ。此外，在分离空间中抗原阳性和抗原阴性肿瘤细胞的肿瘤图像显示，IFN-γ信号的传播范围超过 800 微米。值得注意的是，长距离感知的 IFN-γ可以修改肿瘤行为，如诱导 PD-L1 表达和抑制肿瘤生长。综上所述，这些数据揭示了 CD8+ T 细胞通过 IFN-γ调节远程肿瘤细胞行为的方式，包括抗原丢失变体。