Dissecting the tumor microenvironment in response to immune checkpoint inhibitors via single-cell and spatial transcriptomics

IF 4.2 3区 医学 Q2 ONCOLOGY
Wendi Liu, Anusha Puri, Doris Fu, Lee Chen, Cassia Wang, Manolis Kellis, Jiekun Yang
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引用次数: 0

Abstract

Cancer is a disease that undergoes selective pressure to evolve during its progression, becoming increasingly heterogeneous. Tumoral heterogeneity can dictate therapeutic response. Transcriptomics can be used to uncover complexities in cancer and reveal phenotypic heterogeneity that affects disease response. This is especially pertinent in the immune microenvironment, which contains diverse populations of immune cells, and whose dynamic properties influence disease response. The recent development of immunotherapies has revolutionized cancer therapy, with response rates of up to 50% within certain cancers. However, despite advances in immune checkpoint blockade specifically, there remains a significant population of non-responders to these treatments. Transcriptomics can be used to profile immune and other cell populations following immune-checkpoint inhibitor (ICI) treatment, generate predictive biomarkers of resistance or response, assess immune effector function, and identify potential immune checkpoints. Single-cell RNA sequencing has offered insight into mRNA expression within the complex and heterogeneous tumor microenvironment at single-cell resolution. Spatial transcriptomics has enabled measurement of mRNA expression while adding locational context. Here, we review single-cell sequencing and spatial transcriptomic research investigating ICI response within a variety of cancer microenvironments.

Abstract Image

通过单细胞和空间转录组学剖析肿瘤微环境对免疫检查点抑制剂的反应
癌症是一种在发展过程中承受选择性压力而不断演变的疾病,其异质性越来越强。肿瘤的异质性可决定治疗反应。转录组学可用于揭示癌症的复杂性,揭示影响疾病反应的表型异质性。这一点在免疫微环境中尤为重要,免疫微环境包含多种免疫细胞群,其动态特性会影响疾病反应。近年来,免疫疗法的发展给癌症治疗带来了革命性的变化,某些癌症的应答率高达 50%。然而,尽管在免疫检查点阻断方面取得了具体进展,但仍有相当一部分人对这些疗法没有反应。转录组学可用于分析免疫检查点抑制剂(ICI)治疗后的免疫细胞群和其他细胞群,生成耐药性或反应的预测性生物标记物,评估免疫效应器功能,并确定潜在的免疫检查点。单细胞 RNA 测序能以单细胞分辨率深入了解复杂而异质的肿瘤微环境中的 mRNA 表达。空间转录组学在测量 mRNA 表达的同时还增加了定位背景。在此,我们回顾了单细胞测序和空间转录组学对各种癌症微环境中 ICI 反应的研究。
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来源期刊
CiteScore
7.80
自引率
5.00%
发文量
55
审稿时长
12 months
期刊介绍: The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
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