Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs.
Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs.
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大肠肿瘤干细胞和免疫细胞在肿瘤发生中的串扰，以及针对大肠肿瘤干细胞的策略。
DOI：
10.1186/s40164-024-00474-x
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发表时间：
2024-01-22
影响因子：
10.9
通讯作者：
Jin, Shuiling
中科院分区：
文献类型：
--
作者：
Zhao, Qi;Zong, Hong;Zhu, Pingping;Su, Chang;Tang, Wenxue;Chen, Zhenzhen;Jin, Shuiling
关键词：
肿瘤免疫治疗已成为治疗结直肠癌的一种有前途的策略，肿瘤免疫治疗后的复发越来越受到关注。肿瘤干细胞（CSCs）是一小部分具有自我更新和分化能力的肿瘤细胞，对传统疗法如放疗和化疗具有抗性。最近，CSC已被证明是免疫治疗后驱动肿瘤复发的细胞。然而，CSC和癌症小生境免疫细胞之间的相互作用在很大程度上是未知的。本文就结直肠肿瘤干细胞、肿瘤干细胞与免疫细胞的相互作用及肿瘤干细胞免疫治疗作一综述。结直肠CSC的特征在于表面标志物如CD 44、CD 133和Lgr 5的稳健表达;干性相关信号传导通路如Wnt/β-连环蛋白、Hippo/Yap 1、Jak/Stat和Notch通路的过度活化;以及无序的表观遗传修饰，包括DNA甲基化、组蛋白修饰、染色质重塑和非编码RNA作用。此外，结直肠CSC表达异常水平的免疫相关基因，如MHC和免疫检查点分子，并在多个肿瘤发生相关过程中与癌症小生境细胞相互作用，包括肿瘤起始、维持、转移和耐药性。迄今为止，已经评估了许多靶向CSC的疗法，包括单克隆抗体、抗体药物缀合物、双特异性抗体、肿瘤疫苗、过继细胞疗法和小分子抑制剂。随着CSC-/niche-targeting技术的发展，以及多学科研究的整合，有望开发出消除CSC并逆转其免疫抑制微环境的新疗法用于治疗实体瘤，包括结直肠癌。
Cancer immunotherapy has emerged as a promising strategy in the treatment of colorectal cancer, and relapse after tumor immunotherapy has attracted increasing attention. Cancer stem cells (CSCs), a small subset of tumor cells with self-renewal and differentiation capacities, are resistant to traditional therapies such as radiotherapy and chemotherapy. Recently, CSCs have been proven to be the cells driving tumor relapse after immunotherapy. However, the mutual interactions between CSCs and cancer niche immune cells are largely uncharacterized. In this review, we focus on colorectal CSCs, CSC-immune cell interactions and CSC-based immunotherapy. Colorectal CSCs are characterized by robust expression of surface markers such as CD44, CD133 and Lgr5; hyperactivation of stemness-related signaling pathways, such as the Wnt/β-catenin, Hippo/Yap1, Jak/Stat and Notch pathways; and disordered epigenetic modifications, including DNA methylation, histone modification, chromatin remodeling, and noncoding RNA action. Moreover, colorectal CSCs express abnormal levels of immune-related genes such as MHC and immune checkpoint molecules and mutually interact with cancer niche cells in multiple tumorigenesis-related processes, including tumor initiation, maintenance, metastasis and drug resistance. To date, many therapies targeting CSCs have been evaluated, including monoclonal antibodies, antibody‒drug conjugates, bispecific antibodies, tumor vaccines adoptive cell therapy, and small molecule inhibitors. With the development of CSC-/niche-targeting technology, as well as the integration of multidisciplinary studies, novel therapies that eliminate CSCs and reverse their immunosuppressive microenvironment are expected to be developed for the treatment of solid tumors, including colorectal cancer.
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