缺氧损害了胰腺癌症中CD8+T细胞的适应性，并与功能紊乱的CD8+T电池状态相关
{"_":"Hypoxia Impairs CD8 T Cell Fitness and Is Associated with a Dysfunctional CD8 T Cell State in Pancreatic Cancer.","sup":["+","+"]}
摘要(中文译文)
胰腺导管腺癌（PDAC）以致密的间质微环境和显著的低氧为特征，二者共同导致治疗耐药。利用包含胰腺癌细胞和癌症相关成纤维细胞（CAFs）的体外系统，我们发现低氧抑制CD8 T细胞的积聚，并与癌细胞及CAF来源的因子共同作用，通过增加细胞死亡和减少增殖进一步损害T细胞的功能适应性。尽管低氧与癌细胞/CAF来源因子的联合作用在单细胞水平上增强了CD8 T细胞中IFNγ和颗粒酶B的表达，但功能性效应T细胞的总体数量显著减少。对人PDAC单细胞RNA测序数据的分析证实了这些发现，揭示富集低氧特征的CD8 T细胞表现出凋亡和应激反应通路的升高。此外，低氧与干性相关基因的下调和终末分化标志物的上调相关。综上所述，这些数据表明，内在低氧反应与来自肿瘤细胞和CAFs的外在信号的整合损害了CD8 T细胞的功能适应性，并与终末分化的功能障碍性T细胞状态相关。
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stromal microenvironment and profound hypoxia, which contribute to therapeutic resistance. Using an in vitro system incorporating pancreatic cancer cells and cancer-associated fibroblasts (CAFs), we show that hypoxia suppresses CD8 T cell accumulation and, in combination with cancer cell- and CAF-derived factors, further impairs T cell fitness by increasing cell death and reducing proliferation. Although the combination of hypoxia and cancer cell/CAF-derived factors enhances IFNγ and granzyme B expression in CD8 T cells on a per-cell basis, the overall number of functional effector T cells is markedly reduced. Analysis of human PDAC single-cell RNA sequencing data corroborates these findings, revealing that CD8 T cells enriched for hypoxia signatures exhibit elevated apoptosis and stress-response pathways. Furthermore, hypoxia is associated with downregulation of stemness-related genes and upregulation of terminal differentiation markers. Together, these data suggest that the integration of intrinsic hypoxic responses and extrinsic cues from tumor cells and CAFs impairs CD8 T cell fitness and correlates with a terminally differentiated, dysfunctional T cell state.
如何引用
AMA
Ashley M Mello, Marina Pasca di Magliano, Kyoung Eun Lee. {"_":"Hypoxia Impairs CD8 T Cell Fitness and Is Associated with a Dysfunctional CD8 T Cell State in Pancreatic Cancer.","sup":["+","+"]}. Cancers. 2026; doi:10.3390/cancers18101508.
APA
Ashley M Mello, Marina Pasca di Magliano, Kyoung Eun Lee (2026). {"_":"Hypoxia Impairs CD8 T Cell Fitness and Is Associated with a Dysfunctional CD8 T Cell State in Pancreatic Cancer.","sup":["+","+"]}. Cancers. https://doi.org/10.3390/cancers18101508
GB/T 7714
Ashley M Mello, Marina Pasca di Magliano, Kyoung Eun Lee. {"_":"Hypoxia Impairs CD8 T Cell Fitness and Is Associated with a Dysfunctional CD8 T Cell State in Pancreatic Cancer.","sup":["+","+"]}[J]. Cancers, 2026 doi:10.3390/cancers18101508.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出