Sutton Thomas L, Patel Ranish K, Anderson Ashley N, Bowden Stephen G, Whalen Riley, Giske Nicole R, Wong Melissa H
Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA.
Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97201, USA.
Cancers (Basel). 2022 Aug 11;14(16):3871. doi: 10.3390/cancers14163871.
Cancer remains a significant cause of mortality in developed countries, due in part to difficulties in early detection, understanding disease biology, and assessing treatment response. If effectively harnessed, circulating biomarkers promise to fulfill these needs through non-invasive "liquid" biopsy. While tumors disseminate genetic material and cellular debris into circulation, identifying clinically relevant information from these analytes has proven difficult. In contrast, cell-based circulating biomarkers have multiple advantages, including a source for tumor DNA and protein, and as a cellular reflection of the evolving tumor. While circulating tumor cells (CTCs) have dominated the circulating cell biomarker field, their clinical utility beyond that of prognostication has remained elusive, due to their rarity. Recently, two novel populations of circulating tumor-immune hybrid cells in cancer have been characterized: cancer-associated macrophage-like cells (CAMLs) and circulating hybrid cells (CHCs). CAMLs are macrophage-like cells containing phagocytosed tumor material, while CHCs can result from cell fusion between cancer and immune cells and play a role in the metastatic cascade. Both are detected in higher numbers than CTCs in peripheral blood and demonstrate utility in prognostication and assessing treatment response. Additionally, both cell populations are heterogeneous in their genetic, transcriptomic, and proteomic signatures, and thus have the potential to inform on heterogeneity within tumors. Herein, we review the advances in this exciting field.
在发达国家，癌症仍是一个重要的死亡原因，部分原因在于早期检测、理解疾病生物学以及评估治疗反应存在困难。如果能有效利用，循环生物标志物有望通过非侵入性的“液体”活检满足这些需求。虽然肿瘤会将遗传物质和细胞碎片释放到循环系统中，但从这些分析物中识别出临床相关信息已被证明具有难度。相比之下，基于细胞的循环生物标志物具有多种优势，包括作为肿瘤DNA和蛋白质的来源，以及作为不断演变的肿瘤的细胞反映。虽然循环肿瘤细胞（CTC）在循环细胞生物标志物领域占据主导地位，但由于其稀有性，其在预后之外的临床应用仍难以捉摸。最近，癌症中两种新型的循环肿瘤-免疫杂交细胞群体已被鉴定出来：癌症相关巨噬细胞样细胞（CAML）和循环杂交细胞（CHC）。CAML是含有吞噬肿瘤物质的巨噬细胞样细胞，而CHC可能由癌症细胞与免疫细胞融合产生，并在转移级联反应中发挥作用。在外周血中检测到的这两种细胞数量均高于CTC，并且在预后评估和治疗反应评估中显示出应用价值。此外，这两种细胞群体在基因、转录组和蛋白质组特征方面均具有异质性，因此有可能揭示肿瘤内部的异质性。在此，我们综述了这一令人兴奋的领域的进展。
