From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy.
From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy.
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DOI：
10.3390/molecules26082278
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发表时间：
2021-04-14
期刊：
影响因子：
--
通讯作者：
Baradaran B
中科院分区：
文献类型：
--
作者：
Derakhshani A;Rostami Z;Safarpour H;Shadbad MA;Nourbakhsh NS;Argentiero A;Taefehshokr S;Tabrizi NJ;Kooshkaki O;Astamal RV;Singh PK;Taefehshokr N;Alizadeh N;Silvestris N;Baradaran B
在过去的十年中，在理解癌症发展中涉及的信号通路方面取得了显着的进展。众所周知，癌症是由参与增殖、细胞周期、凋亡、细胞代谢、迁移、细胞极性和分化的细胞途径的失调引起的。此外，越来越多的证据表明，细胞外基质信号，细胞表面蛋白多糖和血管生成可以有助于癌症的发展。鉴于肿瘤细胞的单细胞测序揭示的遗传不稳定性和巨大的肿瘤内异质性，目前的方法无法消除突变的癌细胞。此外，由于免疫抑制性肿瘤微环境，肿瘤浸润淋巴细胞响应肿瘤新抗原的多克隆扩增不能引起抗肿瘤免疫应答。尽管如此，来自免疫细胞的单细胞测序的数据可以提供关于免疫细胞中抑制性免疫检查点/相关信号传导因子表达的有价值的见解，这些见解可用于选择免疫检查点抑制剂并调整其剂量。事实上，将从免疫细胞的单细胞测序获得的数据与免疫检查点抑制剂整合可以提高免疫检查点抑制剂的应答率，减少免疫相关的不良事件，并促进肿瘤细胞消除。本研究旨在回顾肿瘤发展中的关键途径，并阐明单细胞测序。它还打算解决免疫检查点抑制剂的缺点，即，通过应用免疫细胞单细胞测序的数据，他们在癌症患者中的不同反应率和自身免疫发展的风险增加。
Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.
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影响因子：
10.5
作者：
Diehl, JA;Zindy, F;Sherr, CJ
通讯作者：
Sherr, CJ
影响因子：
7.3
作者：
Albini A;Bruno A;Noonan DM;Mortara L
通讯作者：
Mortara L
影响因子：
5.9
作者：
Borcherding N;Vishwakarma A;Voigt AP;Bellizzi A;Kaplan J;Nepple K;Salem AK;Jenkins RW;Zakharia Y;Zhang W
通讯作者：
Zhang W
DOI：
10.1007/978-1-4614-0899-4_15
发表时间：
2012-01-01
期刊：
NOTCH SIGNALING IN EMBRYOLOGY AND CANCER
影响因子：
--
作者：
Dang, Thao P.
通讯作者：
Dang, Thao P.
影响因子：
7.2
作者：
Devreotes, Peter;Horwitz, Alan Rick
通讯作者：
Horwitz, Alan Rick