肿瘤细胞治疗研究
英文原题：A Spatial Multi-Omic Framework Identifies Gliomas Permissive to TIL Expansion.
TIL（肿瘤浸润淋巴细胞）疗法近期获 FDA 批准用于黑色素瘤，是一种新兴的细胞免疫治疗模式。
近期获FDA批准用于黑色素瘤的TIL（肿瘤浸润淋巴细胞）疗法，是一种新兴的细胞免疫治疗方式。然而，由于T细胞浸润稀少、抗原异质性和免疫抑制性肿瘤微环境，其在胶质母细胞瘤等免疫“冷”肿瘤中的应用仍有限。为确定TIL扩增能力的基因组和空间决定因素，我们对高级别胶质瘤开展了整合多模态分析，采用光谱流式细胞术、TCR测序、单细胞RNA测序、Xenium原位转录组学和CODEX空间蛋白质组学。对可产生TIL（TIL+）与不可产生TIL（TIL−）的肿瘤进行比较发现，IL7R表达、结构化的血管周围免疫细胞聚集，以及ACSS3等肿瘤内在代谢程序与成功扩增TIL相关。相反，TIL−肿瘤富集神经元谱系特征、包括TOX和FERMT1在内的免疫抑制性转录本，以及与肿瘤相连的巨噬细胞。本研究界定了TIL制备成功的空间和分子相关特征，并建立了基因组学支持的过继T细胞治疗筛选平台。目前，这一分析方法正在GIANT临床试验（NCT06816927）中前瞻性实施，体现了其转化价值，并显示出在胶质母细胞瘤及其他免疫排斥型癌症中的推广潜力。
Tumor-infiltrating lymphocyte (TIL) therapy, recently approved by the FDA for melanoma, is an emerging modality for cell-based immunotherapy. However, its application in immunologically "cold" tumors such as glioblastoma remains limited due to sparse T cell infiltration, antigenic heterogeneity, and a suppressive tumor microenvironment. To identify genomic and spatial determinants of TIL expandability, we performed integrated, multimodal profiling of high-grade gliomas using spectral flow cytometry, TCR sequencing, single-cell RNA-seq, Xenium in situ transcriptomics, and CODEX spatial proteomics. Comparative analysis of TIL-generating (TIL + ) versus non-generating (TIL - ) tumors revealed that IL7R expression, structured perivascular immune clustering, and tumor-intrinsic metabolic programs such as ACSS3 were associated with successful TIL expansion. In contrast, TIL - tumors were enriched for neuronal lineage signatures, immunosuppressive transcripts including TOX and FERMT1 , and tumor-connected macrophages. This study defines spatial and molecular correlates of TIL manufacturing success and establishes a genomics-enabled selection platform for adoptive T cell therapy. The profiling approach is now being prospectively implemented in the GIANT clinical trial (NCT06816927), supporting its translational relevance and scalability across glioblastoma and other immune-excluded cancers.
MEMBER ACCOUNT
登录成功会直接打开下一页。
