休眠癌症干细胞（DCSC）具有化疗耐药和免疫逃逸的特性，是肿瘤复发和转移的重要来源。然而，潜在的机制仍未被揭示。我们证明食管 DCSC 微环境中富集的 Gzmk CD8 T 细胞限制了肿瘤块的生长。尽管如此，DCSCs 可以通过增强 PD-L1 信号传导来逃避免疫消除，从而维持免疫平衡。静态成纤维细胞来源的静息蛋白巯基氧化酶 1 (QSOX1) 通过提高活性氧水平来促进 DCSC 中 PD-L1 的表达及其自身的表达。此外，休眠肿瘤微环境中的高 QSOX1 有助于排除 CD8 T 细胞。相反，用Ebselen阻断QSOX1并结合抗PD-1和化疗可以通过减少PD-L1表达和促进CD8 T细胞浸润来有效根除残留的DCSC。临床上，QSOX1的高表达预示着食管癌患者对抗PD-1治疗的反应较差。因此，我们的研究结果揭示了 QSOX1 促进 PD-L1 上调和 T 细胞排斥，促进 DCSC 免疫逃逸的机制，而 QSOX1 抑制与免疫疗法和化疗相结合，代表了一种消除 DCSC 和预防复发的有前途的治疗方法。

Dormant cancer stem cells (DCSCs) exhibit characteristics of chemotherapy resistance and immune escape, and they are a crucial source of tumor recurrence and metastasis. However, the underlying mechanisms remain unrevealed. We demonstrate that enriched Gzmk+ CD8+ T cells within the niche of esophageal DCSCs restrict the outgrowth of tumor mass. Nonetheless, DCSCs can escape immune elimination by enhancing PD-L1 signaling, thereby maintaining immune equilibrium. Quiescent fibroblast-derived quiescin sulfhydryl oxidase 1 (QSOX1) promotes the expression of PD-L1 and its own expression in DCSCs by elevating the level of reactive oxygen species. Additionally, high QSOX1 in the dormant tumor niche contributes to the exclusion of CD8+ T cells. Conversely, blocking QSOX1 with Ebselen in combination with anti-PD-1 and chemotherapy can effectively eradicate residual DCSCs by reducing PD-L1 expression and promoting CD8+ T cell infiltration. Clinically, high expression of QSOX1 predicts a poor response to anti-PD-1 treatment in patients with esophageal cancer. Thus, our findings reveal a mechanism whereby QSOX1 promotes PD-L1 upregulation and T cell exclusion, facilitating the immune escape of DCSCs, and QSOX1 inhibition, combined with immunotherapy and chemotherapy, represents a promising therapeutic approach for eliminating DCSCs and preventing recurrence.