一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The role of stem cells in small-cell lung cancer: evidence from chemoresistance to immunotherapy.
The role of stem cells in small-cell lung cancer: evidence from chemoresistance to immunotherapy.
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小细胞肺癌(SCLC)是肺癌中最具侵袭性的亚型,约占所有肺癌的15%。尽管化疗作为SCLC的一线治疗能够迅速缩小肿瘤,但几乎所有患者在数月内都会出现复发和转移。肿瘤干细胞(CSCs)是一小群肿瘤细胞,负责肿瘤发生、转移和治疗后复发,通过促进DNA修复和耐药相关蛋白的表达在化疗耐药中发挥关键作用。
因此,靶向CSCs在某些恶性肿瘤中已取得成功。肿瘤治疗已进入免疫治疗时代,大量临床前试验已证明靶向CSCs的免疫治疗方法(如肿瘤疫苗和嵌合抗原受体(CAR)T细胞)的有效性,以及其与化疗联合的可行性。
因此,深入理解CSCs与免疫系统之间的相互作用对于推动靶向CSCs的新型免疫治疗方法及其与化疗等标准药物联合应用的发展至关重要。本叙述性综述总结了SCLC中CSCs的化疗耐药机制及靶向治疗的最新进展。随后,我们讨论了CSCs对SCLC肿瘤免疫微环境的影响及相应的免疫治疗策略。
最后,我们提出靶向CSCs的免疫治疗与标准药物的联合是SCLC治疗的一个有前景的方向。
Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer, accounting for approximately 15% among all lung cancers. Despite the ability of chemotherapy, the first-line treatment for SCLC, to rapidly shrink tumors, nearly all patients experience recurrence and metastasis within a few months.
Cancer stem cells (CSCs) are a small population of tumor cells responsible for tumorigenesis, metastasis, and recurrence after treatment, which play a crucial role in chemoresistance by promoting DNA repair and expression of drug resistance-associated proteins.
Thus, targeting CSCs has been successful in certain malignancies. Tumor therapy has entered the era of immunotherapy and numerous preclinical trials have demonstrated the effectiveness of immunotherapeutic approaches targeting CSCs, such as tumor vaccines and chimeric antigen receptor (CAR) T cell, and the feasibility of combining them with chemotherapy.
Therefore, a deeper understanding of the interaction between CSCs and immune system is essential to facilitate the advances of new immunotherapies approaches targeting CSCs as well as combination with standard drugs such as chemotherapy. This narrative review summarizes the mechanisms of chemoresistance of CSCs in SCLC and the latest advances in targeted therapies.
Thereafter, we discuss the effects of CSCs on tumor immune microenvironment in SCLC and corresponding immunotherapeutic approaches. Eventually, we propose that the combination of immunotherapy targeting CSCs with standard drugs is a promising direction for SCLC therapies.
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