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在单细胞分辨率上解读结直肠癌免疫微环境转录景观——免疫治疗的作用

英文原题:Deciphering colorectal cancer immune microenvironment transcriptional landscape on single cell resolution - A role for immunotherapy.

查看英文原题

Deciphering colorectal cancer immune microenvironment transcriptional landscape on single cell resolution - A role for immunotherapy.

PubMed 2022/08/10(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

单细胞RNA测序(scRNA-seq)是一种新颖的高通量技术,能够研究单个细胞的整个转录组。它阐明了复杂的细胞网络,并生成最终将有助于开发更具针对性和个性化药物的指标。scRNA-seq的重要性已在癌症和免疫系统等表现出显著细胞异质性的复杂生物系统中得到凸显。结直肠癌(CRC)是全球第三大常见癌症类型,也是癌症相关死亡的第二大原因。化疗仍被用于治疗这些患者。

然而,自20世纪60年代以来,5-FU一直与奥沙利铂和伊立替康联合用于化疗方案中,至今仍在使用。此外,预后不良的化疗耐药转移性CRC已采用单克隆抗体、免疫检查点抑制剂、过继细胞疗法和癌症疫苗等免疫疗法进行治疗。利用肿瘤特异性新抗原的个性化免疫疗法可以将每位患者视为一个独立的组别。在过去十年中,测序和多组学方法帮助我们更精确地识别患者。现代方法的引入和基于新抗原的免疫疗法可能开启治疗CRC的新时代。尚未实现的目标是更好地理解导致CRC发病机制和治疗耐药的细胞和分子机制,识别新的治疗靶点,并利用单细胞方法做出更具分层性和知情性的治疗决策。本综述总结了当前scRNA-seq在CRC研究中的应用,探讨其在开发CRC精准免疫疗法中的潜在效用。

展开英文摘要原文

Single cell RNA sequencing (scRNA-seq) is a novel high-throughput technique that enables the investigation of a single cell's entire transcriptome. It elucidates intricate cellular networks and generates indices that will eventually enable the development of more targeted and personalized medications.

The importance of scRNA-seq has been highlighted in complex biological systems such as cancer and the immune system, which exhibit significant cellular heterogeneity. Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related death globally. Chemotherapy continues to be used to treat these patients.

However, 5-FU has been utilized in chemotherapy regimens with oxaliplatin and irinotecan since the 1960s and is still used today.

Additionally, chemotherapy-resistant metastatic CRCs with poor prognoses have been treated with immunotherapy employing monoclonal antibodies, immune checkpoint inhibitors, adoptive cell therapy and cancer vaccines. Personalized immunotherapy employing tumor-specific neoantigens allows for treating each patient as a distinct group. Sequencing and multi-omics approaches have helped us identify patients more precisely in the last decade.

The introduction of modern methods and neoantigen-based immunotherapy may usher in a new era in treating CRC. The unmet goal is to better understand the cellular and molecular mechanisms that contribute to CRC pathogenesis and resistance to treatment, identify novel therapeutic targets, and make more stratified and informed treatment decisions using single cell approaches. This review summarizes current scRNA-seq utilization in CRC research, examining its potential utility in the development of precision immunotherapy for CRC.

论文信息

作者
Tieng FYF、Lee LH、Ab Mutalib NS
单位
Universiti Kebangsaan Malaysia (UKM) Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.Malaysia
文献类型
综述 · 非美国政府资助研究
期刊
Frontiers in immunology2022
原文标识
PubMed 36032085 · DOI 10.3389/fimmu.2022.959705