癌症干细胞标志物：化学抗药性和免疫逃逸的交响指挥者
Cancer Stem Cell markers: Symphonic masters of chemoresistance and immune evasion
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影响因子:5.1
分区:医学3区 / 药学2区 医学：研究与实验3区
发表日期:2024 Oct 15
作者:
Miguel Angel Sarabia-Sánchez, José Manuel Tinajero-Rodríguez, Elizabeth Ortiz-Sánchez, Eduardo Alvarado-Ortiz
DOI:
10.1016/j.lfs.2024.123015
摘要
癌症干细胞（CSCs）具有高度的肿瘤发生能力、抗化疗性和免疫逃逸能力，成为导致肿瘤大量形成、改变肿瘤微环境（TME）并利用其的核心驱动力，导致癌症患者临床预后不良。因此，CSC的存在解释了传统治疗和免疫监视失败的原因。在现代肿瘤学中，识别实体瘤中的CSC仍然是一大挑战，利用细胞表面标志物是研究、分离和富集这些细胞的主要策略。本综述探讨CSC标志物，重点关注驱动CSC自我更新的信号通路，这些通路使其具有内在的抗化疗性和免疫逃逸能力。我们全面讨论CSC的自主和非自主功能，特别强调其与肿瘤微环境，尤其是免疫细胞的相互作用。这种互惠网络增强CSC的恶性程度，同时破坏周围的微环境，最终揭示每个CSC标志物相关的治疗弱点。本文主要讨论的CSC表面标志物包括CD44、CD133、ICAM1/CD54和LGR5，这些标志物为理解抗化疗性和免疫逃逸的相互关系提供了洞见，这两个现象在疾病根除中具有关键作用。这一前沿视角无疑为未来的治疗开辟了新途径。
Abstract
Cancer Stem Cells (CSCs) are highly tumorigenic, chemoresistant, and immune evasive. They emerge as a central driver that gives rise to the bulk of tumoral mass, modifies the tumor microenvironment (TME), and exploits it, leading to poor clinical outcomes for patients with cancer. The existence of CSCs thus accounts for the failure of conventional therapies and immune surveillance. Identifying CSCs in solid tumors remains a significant challenge in modern oncology, with the use of cell surface markers being the primary strategy for studying, isolating, and enriching these cells. In this review, we explore CSC markers, focusing on the underlying signaling pathways that drive CSC self-renewal, which simultaneously makes them intrinsically chemoresistant and immune system evaders. We comprehensively discuss the autonomous and non-autonomous functions of CSCs, with particular emphasis on their interactions with the tumor microenvironment, especially immune cells. This reciprocal network enhances CSCs malignancy while compromising the surrounding niche, ultimately defining therapeutic vulnerabilities associated with each CSC marker. The most common CSCs surface markers addressed in this review-CD44, CD133, ICAM1/CD54, and LGR5-provide insights into the interplay between chemoresistance and immune evasion, two critically important phenomena in disease eradication. This new perspective on the state-of-the-art of CSCs will undoubtedly open new avenues for therapy.