肿瘤中耗竭性CD8 T细胞效应功能层的多模态描绘。
Multimodal delineation of a layer of effector function among exhausted CD8 T cells in tumors.
作者信息
Ray Arja, Bassette Molly, Hu Kenneth H, Pass Lomax F, Courau Tristan, Samad Bushra, Combes Alexis J, Johri Vrinda, Davidson Brittany, Wai Katherine, Ha Patrick, Hernandez Grace, Zaleta-Linares Itzia, Krummel Matthew F
机构信息
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
ImmunoX Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Sci Immunol. 2025 Jul 11;10(109):eadt3537. doi: 10.1126/sciimmunol.adt3537.
Undescribed functional axes may intersect with the trajectory of T cell exhaustion (T) to contribute to the antitumoral functions of CD8 T cells. By leveraging fluorescent transcriptional reporting of the T cell activation marker , we defined a classifier for potent versus suboptimal CD69 activation states arising from T cell stimulation. In tumors, this delineation provided an additional functional readout among T subsets, marked by enhanced effector molecule production. The more potent -TFP state was the most prominent in a T cell-mediated tumor clearance model, displaying increased engagement and superior tumor cell killing. Simultaneous analysis of gene and protein expression in human head and neck tumors enabled a similar strategy to identify RNACD69 cells with enhanced functional features compared with RNACD69 cells among intratumoral CD8 T cell subsets. Thus, refining the T cell functional landscape in tumors potentiates the identification of rare, potent effectors that could be leveraged for improving cancer treatment.
未描述的功能轴可能与T细胞耗竭(T)轨迹相交,以促进CD8 T细胞的抗肿瘤功能。通过利用T细胞激活标志物的荧光转录报告,我们定义了一种分类器,用于区分由T细胞刺激引起的有效与次优CD69激活状态。在肿瘤中,这种划分在T细胞亚群中提供了额外的功能读数,其特征是效应分子产生增强。在T细胞介导的肿瘤清除模型中,更强效的-TFP状态最为突出,表现出更高的参与度和更好的肿瘤细胞杀伤能力。对人头颈部肿瘤中的基因和蛋白质表达进行同步分析,使得能够采用类似策略,在肿瘤内CD8 T细胞亚群中识别出与RNACD69细胞相比具有增强功能特征的RNACD69细胞。因此,细化肿瘤中的T细胞功能格局有助于识别可用于改善癌症治疗的罕见强效效应细胞。
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