人乳头瘤病毒感染引起的慢性炎症是宫颈癌（CC）发生的重要因素；因此，破译免疫耐受建立过程中肿瘤微环境和先天免疫细胞之间的串扰对于确定潜在的治疗策略至关重要。 单细胞 RNA 测序数据和来自 CC 患者的原发性肿瘤样本用于评估 Siglec 的功能作用-10 树突状细胞 (DC)。患者来源的肿瘤片段平台用于检查 Siglec-10 阻断重振 DC 介导的 T 细胞激活和肿瘤清除的能力。在这里，我们证明 Siglec-10 是浸润在 CC 中的 DC 的重要抑制检查点。 CC上皮细胞利用其异常的表面唾液酸化结构诱导传统DC转化为低免疫原性和高免疫耐受性的表型。此外，Siglec-10 DC 通过 galectin-9 信号传导抑制适应性 T 细胞的功能，从而增强免疫抑制性 CC 微环境。 Siglec-10 信号传导的干扰恢复了 DC 介导的杀肿瘤反应，并增加了适应性 T 细胞对程序性细胞死亡蛋白 1 抑制的敏感性。我们的研究证实了 Siglec-10 对 DC 的检查点作用，并提出靶向 Siglec-10 可能是一种有前途的方法针对 CC 的免疫治疗途径。© 作者（或其雇主）2024。根据 CC BY-NC 允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

The occurrence of chronic inflammation resulting from infection with human papillomaviruses is an important factor in the development of cervical cancer (CC); thus, deciphering the crosstalk between the tumor microenvironment and innate immune cells during the establishment of immune tolerance is vital for identifying potential treatment strategies.Single-cell RNA sequencing data and primary tumor samples from patients with CC were used to evaluate the functional role of Siglec-10 on dendritic cells (DCs). Patient-derived tumor fragment platforms were used to examine the ability of Siglec-10 blockade to reinvigorate DC-mediate T-cell activation and tumor clearance.Here, we demonstrated that Siglec-10 is a prominent inhibitory checkpoint for DCs infiltrated in CC. CC epithelial cells use their aberrant surface sialylated structures to induce the transformation of conventional DCs into phenotypes characterized by low immunogenicity and high immunotolerance. Additionally, Siglec-10+ DCs suppress the function of adaptive T cells via galectin-9 signaling to strengthen the immunosuppressive CC microenvironment. Disturbance of Siglec-10 signaling restored the DC-mediated tumoricidal response and increased adaptive T cells sensitivity to programmed cell death protein 1 inhibition.Our study confirms the checkpoint role of Siglec-10 on DCs and proposes that targeting Siglec-10 may be a promising avenue for immunotherapy against CC.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.