CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.
Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.
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高级别浆液性卵巢癌（HGSOC）起源于输卵管（FT）前体细胞。然而，癌前病变进展为HGSOC过程中发生的分子变化尚不明确。为解决这一问题，我们整合了高多重成像和空间转录组学，分析了HGSOC发展不同阶段的人体组织样本，包括p53印记、浆液性输卵管上皮内癌（STIC）和浸润性HGSOC。我们的研究结果揭示了前体上皮内的免疫调节机制，其特征为染色体不稳定、持续性干扰素（IFN）信号传导以及固有免疫和适应性免疫失调。FT前体显示MHC-I类分子（包括HLA-E）和IFN刺激基因表达升高，这些通常与晚期肿瘤发生相关。这些分子改变与肿瘤微环境的渐进性转变相吻合，从早期STIC中的免疫监视转变为晚期STIC和癌症中的免疫抑制。这些发现确定了HGSOC拦截的潜在生物标志物和治疗靶点，并阐明了从癌前病变到癌症的分子转变。
High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors.
However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC.
Our findings reveal immune modulating mechanisms within precursor epithelium, characterized by chromosomal instability, persistent interferon (IFN) signaling, and dysregulated innate and adaptive immunity. FT precursors display elevated expression of MHC-class I, including HLA-E, and IFN-stimulated genes, typically linked to later-stage tumorigenesis.
These molecular alterations coincide with progressive shifts in the tumor microenvironment, transitioning from immune surveillance in early STICs to immune suppression in advanced STICs and cancer. These insights identify potential biomarkers and therapeutic targets for HGSOC interception and clarify the molecular transitions from precancer to cancer.
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