Chinese Medical Journal Study reveals circulating tumor cells' immune evasion strategies

Metastasis accounts for over 90% of cancer-related deaths, making it the most lethal aspect of cancer progression. Circulating tumor cells (CTCs), shed from primary tumors into the bloodstream, are widely regarded as the “seeds” of metastasis. These cells must evade immune surveillance, survive mechanical stresses, and eventually colonize distant organs—a process that remains poorly understood.

A recent review published in the Chinese Medical Journal on August 8, 2025, provides a concise overview of how CTCs evade immune elimination during circulation, highlighting their interactions with immune cells and blood components, and offering insights into potential therapeutic targets. It was authored by a team of scientists, led by Xiaowei Liu from Institute for Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China.

“Circulating tumor cells orchestrate a sophisticated immune defense, engaging with blood cells such as platelets, NK cells, and neutrophils to create a supportive microenvironment for metastasis,” said Xiaowei Liu, the lead author.

The study focuses on the cellular and molecular strategies employed by CTCs to resist immune elimination. It highlights how CTCs interact with various cell types in the blood—including platelets, NK cells, T cells, neutrophils, macrophages, myeloid-derived suppressor cells, other immunocytes, and endothelial cells—to create an environment that facilitates their survival and metastasis.

At the molecular level, CTCs upregulate immune checkpoint ligands (e.g., PD-L1, CD47, HLA-E), downregulate classical MHC-I, interact with platelets, and resist Fas-mediated apoptosis. The formation of multicellular clusters further protects CTCs from immune recognition and anoikis, while the endocytosis of platelets by CTCs allows them to acquire immune-modulating proteins and transcripts. This process enhances their ability to evade immune surveillance and promotes their survival and metastatic potential.

“By unraveling how CTCs evade immune detection and survive in circulation, our review implicates the various innovative treatments targeting these cells—offering hope for effective anti-metastatic therapies in cancer patients,” added Liu.

By summarizing these immune evasion strategies, the article identifies several potential therapeutic approaches—including anti-platelet therapy, immune checkpoint inhibitors, molecular targeted therapy, and cluster-disrupting agents. It also underscores the evolving role of CTCs in clinical oncology, not only as biomarkers for liquid biopsy, but as functional targets for anti-metastatic immunotherapy.

This work offers valuable insights into the dynamic interplay between CTCs and the circulatory microenvironment and provides a foundation for future translational research in cancer metastasis.