Microenvironment crosstalk and immune evasion of circulating tumor cells: From mechanism to clinical significance

Circulating tumor cells (CTCs), shed from the primary malignancies, are regarded as the "seeds" of tumor metastasis. They employ sophisticated strategies to evade immune detection during blood circulation by engaging with various blood components, ultimately facilitating their colonization in distant organs. Elucidating the mechanisms underlying CTC immune evasion may unlock novel immunotherapeutic strategies to prevent tumor metastasis. Recent advancements in CTC isolation and single-cell sequencing have provided insights into their complex microenvironment and immune evasion mechanisms. Many strategies for targeting either CTCs or their associated blood cells have been explored. Here, we systematically delineated the interaction network between CTCs and the diverse blood cells. By elucidating the microenvironmental and biological characteristics of CTCs, we summarize several potential immune evasion mechanisms, including immune checkpoint modulation, CTC clustering, platelet interactions, etc. Additionally, we highlight recent advances in intervention strategies targeting CTCs and the clinical application of CTCs in cancer liquid biopsy.