Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (T_reg) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in T_reg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector T_reg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.

白介素 23 (IL-23) 是一种促炎细胞因子，主要由骨髓细胞产生，可​​促进各种临床前癌症模型中的肿瘤生长，并与不良后果相关。然而，IL-23 如何促进肿瘤生长尚不清楚。在这里，我们发现肿瘤相关巨噬细胞是小鼠和人类肿瘤微环境中 IL-23 的主要来源。在 IL-23 传感细胞中，我们鉴定了肿瘤浸润性调节性 T (T _reg ) 细胞的子集，它们在小鼠和人类肿瘤中表现出高度抑制表型。三种实体癌临床前模型的使用与T _reg细胞中IL23r的基因消融相结合，揭示了它们与 IL-23 的肿瘤促进作用有关。从机制上讲，我们发现 IL-23 传感代表了驱动效应 T _reg细胞维持和稳定的关键信号，涉及转录因子 Foxp3。我们的数据支持，靶向癌症中的 IL-23/IL-23R 轴可能是引发抗肿瘤免疫的一种手段。