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.

T 细胞分泌的干扰素 (IFN)-γ 可以对肿瘤细胞发挥多效作用，包括诱导免疫检查点和抗原呈递机制成分，以及抑制细胞生长。^{尽管它是一个关键效应分子，但对激活的 CD8 +}分泌的 IFN-γ 的时空扩散知之甚少。肿瘤环境中的 T 细胞。使用多日活体成像，我们证明了一小部分肿瘤细胞的 T 细胞识别导致大部分肿瘤块感知到 IFN-γ。此外，抗原阳性和抗原阴性肿瘤细胞在空间中分离的肿瘤成像显示 IFN-γ 反应的扩散，达到 >800 µm 的距离。值得注意的是，IFN-γ 的远程感应可以改变肿瘤行为，如诱导 PD-L1 表达和抑制肿瘤生长所示。总的来说，这些数据揭示了 CD8 ⁺ T 细胞如何通过 IFN-γ 调节远程肿瘤细胞的行为，包括抗原丢失变体。