循环肿瘤细胞(CTCs)首次被描述是在150年前。所谓的“经典”CTC群体(EpCAM+/CK+/CD45-)已被充分表征并被提议作为最具代表性的CTC亚群，具有临床相关性。尽管如此，其他“非典型”或“非常规”的CTCs也被鉴定出，并且其在转移形成中的关键作用得到了证实。在本章中，我们详细介绍了导致非常规CTCs发现的研究，将其定义为显示上皮和间质标记物、或癌症和免疫标记物、以及混合癌症-免疫细胞形式的CTCs。我们还提出了这些非常规CTCs形成的生物学解释：上皮向间质转化、细胞-细胞融合和食细胞作用。我们认为，需要对CTCs的生物学有更深入的了解，以充分阐明它们在癌症进展中的作用以及它们作为癌症生物标志物的应用。版权所有 © 2023 Elsevier Inc. 发布

Circulating tumor cells (CTCs) were first described 150 years ago. The so-called "classical" CTC populations (EpCAM+/CK+/CD45-) have been fully characterized and proposed as the most representative CTC subset, with clinical relevance. Nonetheless, other "atypical" or "unconventional" CTCs have also been identified, and their critical role in metastasis formation was demonstrated. In this chapter we illustrate the studies that led to the discovery of unconventional CTCs, defined as CTCs that display both epithelial and mesenchymal markers, or both cancer and immune markers, also in the form of hybrid cancer-immune cells. We also present biological explanations for the origin of these unconventional CTCs: epithelial to mesenchymal transition, cell-cell fusion and trogocytosis. We believe that a deeper knowledge on the biology of CTCs is needed to fully elucidate their role in cancer progression and their use as cancer biomarkers.Copyright © 2023. Published by Elsevier Inc.