Identification and Study of Immune Checkpoints in Circulating Tumor Cells

Circulating tumor cells (CTCs) are cells isolated from primary tumors and circulating in the bloodstream. As a potentially rich source of information, they can provide insight into tumor biology and progression. Unraveling the immune checkpoints in CTCs provides a deeper and more nuanced understanding.

Creative Biolabs explores immune checkpoints on CTCs, which can provide valuable information about the interactions between cancer cells and the immune system, potentially guiding personalized therapeutic strategies.

Immune Checkpoints and CTCs

CTCs can play an important role in the metastatic spread of cancer by reaching distant sites through the bloodstream and triggering the formation of secondary tumors. Immune cells can recognize and target a small fraction of CTCs for destruction. However, some CTCs may express immune checkpoint ligands that bind to immune checkpoint receptors on immune cells, leading to immunosuppression and reduced tumor cell killing.

Immune checkpoint therapy targeting circulating tumor cells.Fig. 1 Immune checkpoint therapy targeting circulating tumor cells. (Zhong X, et al., 2020)

Researchers are exploring the use of immune checkpoint inhibitors to target CTCs and prevent them from escaping immune surveillance. By blocking the interaction between immune checkpoints on CTCs and immune cells, the immune response against these circulating cancer cells could be enhanced and the risk of metastasis reduced.

Methods for Immune Checkpoint Identification in CTCs

Identifying immune checkpoints in CTCs is a multifaceted and complex affair. First, multiple biomarkers are often employed to distinguish CTCs from normal cells that share their environment. Flow cytometry, digital pathology, and immunocytochemistry are standard techniques in CTC identification. Increasingly, finer techniques are being fully utilized.

  • Cell Capture Technology
    Various technologies such as microfluidic devices, immunomagnetic separation, and size-based filtration have been developed to achieve efficient CTC capture while preserving their molecular characteristics.
  • Single-Cell Analysis
    Single-cell analysis reveals subtle differences in individual CTCs at the single-cell level. The technique helped researchers focus on checkpoint genes and proteins that coordinate immune evasion.
  • Advanced Imaging
    Advanced imaging techniques will enable the visualization of immune checkpoint proteins on CTCs. Using high-resolution microscopy, researchers can study checkpoint distribution and co-expression with other markers, revealing a range of new insights.
  • Multi-omic Approach
    Integrating multiple omics data, such as genomics, transcriptomics, and proteomics, provides a comprehensive view of immune checkpoint regulation in CTCs. This holistic approach enhances our understanding of the underlying molecular mechanisms and identifies potential therapeutic targets.

Challenges and Future Directions

Although the identification of immune checkpoints in CTCs is an emerging field with great potential, several challenges remain.

  • Heterogeneity among CTC populations
  • Technical limitations in capturing and analyzing these rare cells

By elucidating the complex interplay between immune checkpoints and CTCs, researchers are paving the way for personalized therapeutic strategies that exploit these checkpoints to overcome immune evasion. Creative Biolabs is also continuously advancing the immune checkpoint research of CTC.


  1. Zhong X, et al. Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy. Molecular cancer, 2020, 19(1): 1-12.
  2. Rzhevskiy A, et al. Emerging role of circulating tumor cells in immunotherapy. Theranostics, 2021, 11(16): 8057.

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