为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Multi-omics spatial characteristics of CD8(+)TRM cells in hepatocellular carcinoma and immunotherapy response prediction.
Multi-omics spatial characteristics of CD8(+)TRM cells in hepatocellular carcinoma and immunotherapy response prediction.
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免疫治疗可通过调控 CD8+ TRM 细胞与其他免疫细胞的交互作用,改变其空间特征,而 CD8+ TRM 细胞在 HCC 肿瘤微环境(TME)中的空间分布与免疫检查点阻断(ICB)治疗疗效相关。阐明免疫治疗药物的作用机制并开发无创影像组学模型以预测 CD8⁺ TRM 细胞动态变化,将有助于 HCC 的临床管理。
理解肝细胞癌(HCC)中CD8+组织驻留记忆T细胞(TRM)的空间特征具有挑战性,而阐明免疫治疗后空间特征的变化是一个亟待填补的研究空白。
本研究采用多组学方法,利用影像组学、单细胞测序和多重免疫荧光组织化学(m-IHC)分析HCC组织中TRM细胞的空间分布和细胞间相互作用。
我们的结果显示,HCC中CD8 + TRM细胞的数量在免疫治疗后增加。此外,将肿瘤组织分为肿瘤核心(TC)、浸润边缘(IM)和正常组织(N)后,可以观察到CD8 + TRM细胞从IM到TC的增加。与单细胞测序分析结果一致,这种空间特征的变化可能与CD8 + TRM细胞和CD68 + 细胞之间的相互作用有关。
This study employs a multi-omics approach to analyze the spatial distribution and intercellular interactions of TRM cells in HCC tissues using radiomics, single-cell sequencing, and multiplex immunofluorescence histochemistry (m-IHC).
Our results show that the number of CD8 + TRM cells in HCC increases following immunotherapy. Furthermore, after dividing tumor tissues into the tumor core (TC), invasion margin (IM), and normal tissue (N), a increase in CD8 + TRM cells from the IM to the TC can be observed. Consistent with the results of single-cell sequencing analysis, this change in spatial characteristics may be associated with the interactions between CD8 + TRM cells and CD68 + cells. DISCUSSION: Immunotherapy can modify the spatial characteristics of CD8 + TRM cells via regulating their crosstalk with other immune cells, and the spatial distribution of CD8 + TRM cells in the HCC tumor microenvironment (TME) correlates with immune checkpoint blockade (ICB) therapeutic efficacy. Clarifying the mechanisms of action of immunotherapeutic drugs and developing a non-invasive radiomics model to predict CD8⁺ TRM cell dynamics will facilitate the clinical management of HCC.
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