转录因子、免疫检查点抑制剂和干性特征在结直肠癌中复杂的网络:最近的更新。
The complex network of transcription factors, immune checkpoint inhibitors and stemness features in colorectal cancer: A recent update.
发表日期:2023 Feb
作者:
Maysaloun Merhi, Fareed Ahmad, Nassiba Taib, Varghese Inchakalody, Shahab Uddin, Alaaeldin Shablak, Said Dermime
来源:
SEMINARS IN CANCER BIOLOGY
摘要:
癌症免疫是由免疫细胞表达的共刺激和/或共抑制分子所调节的多种机制。在结直肠癌(CRC)中,CTLA-4、LAG3、TIM-3和PD-1是参与肿瘤发展和进展的主要共抑制检查点。另一方面,转录因子的失调和癌细胞干细胞活性在CRC的药物耐受性发展和转移性疾病的扩散中起着重要作用。在本综述中,我们描述了这些转录因子的调节如何影响CRC对治疗的反应。我们还关注癌细胞干细胞在肿瘤转移和化疗抗性中的作用,并讨论了针对干细胞的临床前和临床方法,以防止它们的肿瘤发生效应。最后,我们提供了一份关于免疫检查点抑制剂在CRC中的临床应用的更新,并讨论了转录因子对特定关注PD-1和PD-L1分子的免疫抑制检查点表达的调控作用。 版权所有 ©2023作者。由Elsevier Ltd.出版。保留所有权利。
Cancer immunity is regulated by several mechanisms that include co-stimulatory and/or co-inhibitory molecules known as immune checkpoints expressed by the immune cells. In colorectal cancer (CRC), CTLA-4, LAG3, TIM-3 and PD-1 are the major co-inhibitory checkpoints involved in tumor development and progression. On the other hand, the deregulation of transcription factors and cancer stem cells activity plays a major role in the development of drug resistance and in the spread of metastatic disease in CRC. In this review, we describe how the modulation of such transcription factors affects the response of CRC to therapies. We also focus on the role of cancer stem cells in tumor metastasis and chemoresistance and discuss both preclinical and clinical approaches for targeting stem cells to prevent their tumorigenic effect. Finally, we provide an update on the clinical applications of immune checkpoint inhibitors in CRC and discuss the regulatory effects of transcription factors on the expression of the immune inhibitory checkpoints with specific focus on the PD-1 and PD-L1 molecules.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.