Immunotherapy advances have been hindered by difficulties in tracking the behaviors of lymphocytes after antigen signaling. Here, we assessed the behavior of T cells active within tumors through the development of the antigen receptor signaling reporter (AgRSR) mouse, fate-mapping lymphocytes responding to antigens at specific times and locations. Contrary to reports describing the ready egress of T cells out of the tumor, we find that intratumoral antigen signaling traps CD8⁺ T cells in the tumor. These clonal populations expand and become increasingly exhausted over time. By contrast, antigen-signaled regulatory T cell (T_reg) clonal populations readily recirculate out of the tumor. Consequently, intratumoral antigen signaling acts as a gatekeeper to compartmentalize CD8⁺ T cell responses, even within the same clonotype, thus enabling exhausted T cells to remain confined to a specific tumor tissue site.

中文翻译：

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肿瘤内抗原信号传导捕获 CD8+ T 细胞，将耗竭限制在肿瘤部位


由于追踪抗原信号传导后淋巴细胞行为的困难，免疫疗法的进展受到阻碍。在这里，我们通过开发抗原受体信号报告基因 (AgRSR) 小鼠，评估肿瘤内活跃的 T 细胞的行为，即命运图谱淋巴细胞在特定时间和位置对抗原作出反应。与描述 T 细胞随时从肿瘤中流出的报道相反，我们发现肿瘤内抗原信号传导将 CD8 ⁺ T 细胞捕获在肿瘤中。随着时间的推移，这些克隆种群不断扩大并变得越来越疲惫。相比之下，抗原信号调节性 T 细胞 (T _reg ) 克隆群很容易从肿瘤中再循环。因此，肿瘤内抗原信号传导充当了分隔 CD8 ⁺ T 细胞反应的看门人，即使在同一克隆型内也是如此，从而使耗尽的 T 细胞保持局限于特定的肿瘤组织部位。