肿瘤细胞治疗研究
英文原题：Transcriptomic analysis of tissue-resident memory T cells of the fallopian tube reveals a precursor immune surveillance network for ovarian cancer prevention.
我们发现FT来源的TRML与肿瘤浸润性TRML之间存在显著的克隆和功能重叠（18.4%），超过循环T细胞的重叠程度。
输卵管（FT）日益被认为是高级别浆液性卵巢癌（HGSOC）的起源部位，但其免疫微环境仍知之甚少。在此，我们采用单细胞 RNA 测序和配对 T 细胞受体测序，对来自患者匹配的非癌性 FT、转移性肿瘤和外周血的组织驻留记忆样 T 细胞（TRML）进行了分析。我们鉴定出 FT 来源与肿瘤浸润 TRML 之间存在显著的克隆和功能重叠（18.4%），超过循环 T 细胞。共享克隆型优先富集于耗竭 CD8+ 亚群中，包括一个此前未表征的 SIK3-high 亚群，与表观遗传可塑性和代谢适应相关。在功能上，FT 来源的 TRML 可识别自体肿瘤抗原，在类器官共培养实验中表现出强烈的干扰素-γ（IFN-γ）反应和 CD137 上调，支持其在早期免疫监视中的作用。值得注意的是，FT TRML 的耗竭程度低于肿瘤对应细胞，提示其治疗潜力。这些发现揭示了 FT 中存在一个前体免疫监视网络，并支持利用 FT 驻留 T 细胞进行癌症免疫治疗和预防。
The fallopian tube (FT) is increasingly recognized as the origin of high-grade serous ovarian cancer (HGSOC), yet its immune landscape remains poorly understood. Here, we employ single-cell RNA sequencing and paired T-cell receptor sequencing to profile tissue-resident memory-like T cells (TRML) from patient-derived matched non-cancerous FT, metastatic tumors, and peripheral blood. We identify substantial clonal and functional overlap (18.4%) between FT-derived and tumor-infiltrating TRMLs, exceeding that of circulating T cells. Shared clonotypes are preferentially enriched in exhausted CD8+ subsets, including a previously uncharacterized SIK3-high subset linked to epigenetic plasticity and metabolic adaptation. Functionally, FT-derived TRMLs recognize autologous tumor antigens, showing strong interferon-γ (IFN-γ) responses and CD137 upregulation in organoid coculture assays, supporting a role in early immune surveillance. Notably, FT TRMLs exhibit lower exhaustion than tumor counterparts, suggesting therapeutic potential. These findings reveal a precursor immune surveillance network in the FT and support leveraging FT-resident T cells for cancer immunotherapy and prevention.
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