CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis.
Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis.
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TIL（肿瘤浸润淋巴细胞）（TILs），尤其是 CD8 + TILs，在高浆液性卵巢癌（HGSOC）及其他肿瘤谱系中是预后良好的因素。在此，我们分析了 HGSOC 中不同 TIL 亚型的空间异质性。我们整合了 RNA 测序、全基因组测序、批量 T 细胞受体（TCR）测序以及单细胞 RNA/TCR 测序，以研究不同 HGSOC 部位 TILs 的特征和组成差异。我们确定了卵巢癌中的两种免疫“冷”模式：（1）卵巢病灶以功能失调 T 细胞和免疫抑制性 Treg 细胞低浸润为主；（2）大网膜病灶被非肿瘤特异性旁观者细胞浸润。优先富集于卵巢肿瘤中的耗竭 CD8 T 细胞显示出扩增和细胞毒性活性的证据。固有的肿瘤免疫微环境特征似乎是 TIL 状态空间差异的主要贡献因素。TILs 空间异质性图谱可能为 HGSOC 的治疗干预策略提供信息。
Tumor-infiltrating lymphocytes (TILs), especially CD8 + TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages.
Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC.
We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune "cold" patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells.
Exhausted CD8 T cells that are preferentially enriched in ovarian tumors exhibit evidence for expansion and cytotoxic activity. Inherent tumor immune microenvironment characteristics appear to be the main contributor to the spatial differences in TIL status. The landscape of spatial heterogeneity of TILs may inform potential strategies for therapeutic manipulation in HGSOC.
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