结肠癌是第二常见的相关致死癌症。肠道干细胞负责维持肠内稳态，一旦发生转化，便会成为结肠癌干细胞。阻止癌症干性代表了一种创新的结肠癌管理策略。我们使用肠道干细胞器官样体作为主要模型，对常见的炎症细胞因子进行筛选，以识别靶向癌症干性的关键调节因子。我们还通过实验研究和计算预测探索了相关细胞因子的下游信号传导机制。作为结果，我们确定了IFNγ作为关键的细胞因子，能够通过IFNγ/IFNGR2/APC/TCF4/GPX4轴抑制肠道干细胞，并提出了其通过激活GPX4依赖的铁死亡方式杀灭结肠癌干细胞的作用，并展示了其与冷等离子体具有协同抗癌效应的价值，值得进行实验验证。

Colorectal cancer accounts for the second most common cancer-related lethality. Intestinal stem cells are responsible for enteric homeostasis maintenance that, once being transformed, become colorectal cancer stem cells. Arresting cancer stemness represents an innovative strategy for colorectal cancer management. Using intestinal stem cell organoids as the primary model, we screened common inflammatory cytokines to identify key players targeting cancer stemness. We also explored the downstream signaling that drives the functionalities of the identified cytokine through both experimental investigations and computational predictions. As the results, we identified IFNγ as the key cytokine capable of arresting intestinal stem cells via the IFNγ/IFNGR2/APC/TCF4/GPX4 axis, proposed its role in killing colorectal cancer stem cells via triggering GPX4-dependent ferroptosis, and demonstrated its synergistic anti-cancer effect with cold atmospheric plasma in killing colorectal cancer cells that is worthy to be experimentally validated.