Veschi Veronica, Turdo Alice, Stassi Giorgio
Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, Palermo, Italy.
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.
Front Mol Med. 2023 May 18;3:1120090. doi: 10.3389/fmmed.2023.1120090. eCollection 2023.
Cancer stem cells (CSCs) represent the most aggressive subpopulation present in the tumor bulk retaining invasive capabilities, metastatic potential and high expression levels of drug efflux pumps responsible for therapy resistance. Cancer is still an incurable disease due to the inefficacy of standard regimens that spare this subpopulation. Selective targeting of CSCs is still an unmet need in cancer research field. Aberrant epigenetic reprogramming promotes the initiation and maintenance of CSCs, which are able to escape the immune system defense. Promising therapeutic approaches able to induce the selective inhibition of this stem-like small subset include immunotherapy alone or in combination with epigenetic compounds. These strategies are based on the specific expression of epitopes and/or epigenetic alterations present only in the CSC and not in the other cancer cells or normal cells. Thus, the combined approach utilizing CAR-T immunotherapy along with epigenetic probes may overcome the barriers of treatment ineffectiveness towards a more precision medicine approach in patients with known specific alterations of CSCs. In this perspective article we will shed new lights on the future applications of epi-immunotherapy in tumors enriched in CSCs, along with its potential side-effects, limitations and the development of therapy resistance.
癌症干细胞（CSCs）是肿瘤主体中最具侵袭性的亚群，具有侵袭能力、转移潜能以及负责耐药性的药物外排泵的高表达水平。由于标准治疗方案对该亚群无效，癌症仍然是一种无法治愈的疾病。选择性靶向癌症干细胞仍是癌症研究领域尚未满足的需求。异常的表观遗传重编程促进了癌症干细胞的起始和维持，而癌症干细胞能够逃避免疫系统的防御。能够诱导选择性抑制这种干细胞样小亚群的有前景的治疗方法包括单独的免疫疗法或与表观遗传化合物联合使用。这些策略基于仅在癌症干细胞中而非其他癌细胞或正常细胞中存在的表位的特异性表达和/或表观遗传改变。因此，将嵌合抗原受体T细胞（CAR-T）免疫疗法与表观遗传探针相结合的方法，可能克服在已知癌症干细胞存在特定改变的患者中治疗无效的障碍，从而实现更精准的医学治疗方法。在这篇观点文章中，我们将阐明表观遗传免疫疗法在富含癌症干细胞的肿瘤中的未来应用，以及其潜在的副作用、局限性和治疗耐药性的发展。
