Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh, 202002, India.
Cancer Metastasis Rev. 2024 Mar;43(1):155-173. doi: 10.1007/s10555-023-10141-y. Epub 2023 Sep 30.
Cancer cells undergo phenotypic switching (cancer cell plasticity) in response to microenvironmental cues, including exposure to therapy/treatment. Phenotypic plasticity enables the cancer cells to acquire more mesenchymal traits promoting cancer cells' growth, survival, therapy resistance, and disease recurrence. A significant program in cancer cell plasticity is epithelial-to-mesenchymal transition (EMT), wherein a comprehensive reprogramming of gene expression occurs to facilitate the translational shift from epithelial-to-mesenchymal phenotypes resulting in increased invasiveness and metastasis. In addition, EMT plays a pivotal role in facilitating cancer cells' escape from the body's immune system using several mechanisms, such as the downregulation of major histocompatibility complex-mediated antigen presentation, upregulation of immune checkpoint molecules, and recruitment of immune-suppressive cells. Cancer cells' ability to undergo phenotypic switching and EMT-driven immune escape presents a formidable obstacle in cancer management, highlighting the need to unravel the intricate mechanisms underlying these processes and develop novel therapeutic strategies. This article discusses the role of EMT in promoting immune evasion and therapy resistance. We also discuss the ongoing research on developing therapeutic approaches targeting intrinsic and induced cell plasticity within the immune suppressive microenvironment. We believe this review article will update the current research status and equip researchers, clinicians, and other healthcare professionals with valuable insights enhancing their existing knowledge and shedding light on promising directions for future cancer research. This will facilitate the development of innovative strategies for managing therapy-resistant cancers and improving patient outcomes.
癌细胞会根据微环境线索（包括治疗暴露）发生表型转换（癌细胞可塑性）。表型可塑性使癌细胞获得更多的间充质特征，促进癌细胞的生长、存活、治疗抵抗和疾病复发。癌细胞可塑性的一个重要程序是上皮-间充质转化（EMT），其中基因表达发生全面重编程，促进从上皮到间充质表型的翻译转移，导致侵袭性和转移增加。此外，EMT 通过几种机制在促进癌细胞逃避机体免疫系统方面起着关键作用，例如下调主要组织相容性复合物介导的抗原呈递、上调免疫检查点分子和招募免疫抑制细胞。癌细胞发生表型转换和 EMT 驱动的免疫逃逸的能力是癌症管理中的一个巨大障碍，这突出表明需要揭示这些过程背后的复杂机制，并开发新的治疗策略。本文讨论了 EMT 在促进免疫逃逸和治疗抵抗中的作用。我们还讨论了正在进行的研究，旨在针对免疫抑制微环境中的内在和诱导细胞可塑性开发治疗方法。我们相信，这篇综述文章将更新当前的研究现状，为研究人员、临床医生和其他医疗保健专业人员提供有价值的见解，增强他们现有的知识，并为未来的癌症研究指明有希望的方向。这将有助于开发管理耐药性癌症的创新策略，并改善患者的治疗效果。
