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。
TIL（肿瘤浸润淋巴细胞）疗法近期获美国食品药品监督管理局批准用于黑色素瘤，是一种新兴细胞免疫疗法。然而，由于胶质母细胞瘤等免疫“冷”肿瘤中T细胞浸润稀少、抗原异质性高且肿瘤微环境具有抑制性，TIL疗法在这类肿瘤中的应用仍受限。为鉴定决定TIL可扩增性的基因组和空间因素，研究者采用光谱流式细胞术、TCR测序、单细胞RNA测序、Xenium原位转录组学及CODEX空间蛋白质组学，对高级别胶质瘤进行整合多模态分析。比较可生成TIL（TIL+）与不能生成TIL（TIL−）的肿瘤发现，IL7R表达、结构化血管周围免疫细胞聚集及ACSS3等肿瘤内在代谢程序与TIL成功扩增相关。相反，TIL−肿瘤富集神经元谱系特征、TOX和FERMT1等免疫抑制性转录本以及与肿瘤相关联的巨噬细胞。本研究明确了TIL制备成功的空间和分子相关特征，并建立基因组学支持的过继T细胞治疗患者筛选平台。该分析策略现正前瞻性应用于GIANT临床试验（NCT06816927），体现其转化相关性及在胶质母细胞瘤和其他免疫排斥型癌症中的可扩展性。
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.
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