研究动态
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多参数单细胞蛋白质组技术为卵巢肿瘤生物学提供新的洞见。

Multiparameter single-cell proteomic technologies give new insights into the biology of ovarian tumors.

发表日期:2023 Jan
作者: Ionut-Gabriel Funingana, Jacob S Bedia, Ying-Wen Huang, Antonio Delgado Gonzalez, Kenyi Donoso, Veronica D Gonzalez, James D Brenton, Alan Ashworth, Wendy J Fantl
来源: Seminars in Immunopathology

摘要:

高级别浆液性卵巢癌(HGSOC)是最致命的妇科恶性肿瘤。其在晚期诊断和过多的基因组和细胞异质性的困扰下,使得治疗的彻底性变得非常具有挑战性。克服的两个关键治疗挑战是卡铂抵抗和免疫治疗缺乏反应。卡铂抵抗源于不同组合在肿瘤内外部运作的不同细胞性机制。对免疫治疗缺乏反应高度可能与免疫抑制性的HGSOC肿瘤微环境有关,其覆盖了任何临床上的益处。来自许多研究的结果,主要利用转录组学,表明免疫肿瘤微环境(iTME)在卡铂反应中起着作用。然而,在接受治疗的患者中,确切的机制细节尚不清楚。在过去的十年中,多重单细胞蛋白质组学技术已经成为生物医学研究的前沿。质谱流式细胞术或飞行时间流式细胞术可以测量悬浮单个细胞中的多达60个参数。多重细胞成像技术允许同时测量单个细胞中的多达60种蛋白质,具有空间分辨率和对细胞间相互作用的问询。本综述表明,在卡铂自主反应和HGSOC免疫肿瘤微环境之间的功能性相互作用可能会通过多重单细胞蛋白质组学技术得到澄清。我们得出结论,为了更好的临床护理,多重单细胞蛋白质组学技术可以成为基因组学和放射组学的多模式生物标记物开发的组成部分。收集患者在治疗前和治疗期间的匹配样本对于这些努力的成功至关重要。©2023年作者。
High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy. Its diagnosis at advanced stage compounded with its excessive genomic and cellular heterogeneity make curative treatment challenging. Two critical therapeutic challenges to overcome are carboplatin resistance and lack of response to immunotherapy. Carboplatin resistance results from diverse cell autonomous mechanisms which operate in different combinations within and across tumors. The lack of response to immunotherapy is highly likely to be related to an immunosuppressive HGSOC tumor microenvironment which overrides any clinical benefit. Results from a number of studies, mainly using transcriptomics, indicate that the immune tumor microenvironment (iTME) plays a role in carboplatin response. However, in patients receiving treatment, the exact mechanistic details are unclear. During the past decade, multiplex single-cell proteomic technologies have come to the forefront of biomedical research. Mass cytometry or cytometry by time-of-flight, measures up to 60 parameters in single cells that are in suspension. Multiplex cellular imaging technologies allow simultaneous measurement of up to 60 proteins in single cells with spatial resolution and interrogation of cell-cell interactions. This review suggests that functional interplay between cell autonomous responses to carboplatin and the HGSOC immune tumor microenvironment could be clarified through the application of multiplex single-cell proteomic technologies. We conclude that for better clinical care, multiplex single-cell proteomic technologies could be an integral component of multimodal biomarker development that also includes genomics and radiomics. Collection of matched samples from patients before and on treatment will be critical to the success of these efforts.© 2023. The Author(s).