免疫系统对肿瘤的控制和生长关键决定了患者的命运和生存。目前尚不清楚是什么调节了结肠癌逃脱免疫系统破坏的机制。在这里，我们研究了肠道合成糖皮质激素在炎症诱导的结肠癌小鼠模型中的肿瘤发展角色。我们证明了免疫调节糖皮质激素的局部合成在调节肠炎和肿瘤发展中具有双重作用。在炎症阶段，LRH-1 / Nr5A2调节和Cyp11b1介导的肠道糖皮质激素合成防止肿瘤的发展和生长。然而，在已经形成的肿瘤中，瘤内Cyp11b1介导的糖皮质激素合成抑制抗肿瘤免疫反应并促进免疫逃逸。将能够合成糖皮质激素的结肠癌肿瘤器官移植到免疫能力正常的受体小鼠体内会导致快速肿瘤生长，而Cyp11b1删除和糖皮质激素合成缺陷的肿瘤器官则表现为减少的肿瘤生长和增多的免疫细胞浸润。在人类结肠癌中，类固醇合酶的高表达与其他免疫检查点和抑制性细胞因子的表达相关，并与患者的整体生存率呈负相关。因此，LRH-1调节的肿瘤特异性糖皮质激素合成有助于肿瘤免疫逃逸，并代表一种新的潜在治疗靶点。本文受版权保护。版权所有。

Control of tumor development and growth by the immune system critically defines patient fate and survival. What regulates the escape of colorectal tumors from destruction by the immune system is currently unclear. Here, we investigated the role of intestinal synthesis of glucocorticoids in the tumor development during inflammation-induced mouse model of colorectal cancer. We demonstrate that the local synthesis of immunoregulatory glucocorticoids has dual roles in the regulation of intestinal inflammation and tumor development. In the inflammation phase LRH-1/Nr5A2-regulated and Cyp11b1-mediated intestinal glucocorticoid synthesis prevents tumor development and growth. In established tumors, however, tumor-autonomous Cyp11b1-mediated glucocorticoid synthesis suppresses anti-tumor immune responses and promotes immune escape. Transplantation of glucocorticoid synthesis-proficient colorectal tumor organoids into immunocompetent recipient mice resulted in rapid tumor growth, whereas transplantation of Cyp11b1-deleted and glucocorticoid synthesis-deficient tumor organoids was characterized by reduced tumor growth and increased immune cell infiltration. In human colorectal tumors, high expression of steroidogenic enzymes correlated with the expression of other immune checkpoints and suppressive cytokines, and negatively correlated with overall patients' survival. Thus, LRH-1-regulated tumor-specific glucocorticoid synthesis contributes to tumor immune escape and represents a novel potential therapeutic target.This article is protected by copyright. All rights reserved.