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Spatial heterogeneity of infiltrating T cells in high- grade serous ovarian cancer revealed by multi-omics analysis

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单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Gynecol & Obstet, Wuhan 430030, Peoples R China [3]City Univ Hong Kong, Shenzhen Res Inst, Shenzhen 518083, Peoples R China [4]Oregon Hlth & Sci Univ, Dept Cell Dev & Canc Biol, Portland, OR 97201 USA [5]Knight Canc Inst, Portland, OR 97201 USA [6]Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA
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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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大类 | 1 区 医学
小类 | 1 区 医学:研究与实验 2 区 细胞生物学
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Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan 430030, Peoples R China
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