TRAIL-coated leukocytes to kill circulating tumor cells in the flowing blood from prostate cancer patients

BMC Cancer. 2021 Aug 6;21(1):898. doi: 10.1186/s12885-021-08589-8.


Background: Radical surgery is the first line treatment for localized prostate cancer (PC), however, several studies have demonstrated that surgical procedures induce tumor cell mobilization from the primary tumor into the bloodstream.

Methods: The number and temporal fluctuations of circulating tumor cells (CTC), cancer associated fibroblasts (CAF) and CTC cluster present in each blood sample was determined.

Results: The results show that both CTC and CTC cluster levels significantly increased immediately following primary tumor resection, but returned to baseline within 2 weeks post-surgery. In contrast, the CAF level decreased over time. In patients who experienced PC recurrence within months after resection, CTC, CAF, and cluster levels all increased over time. Based on this observation, we tested the efficacy of an experimental TNF-related apoptosis-inducing ligand (TRAIL)-based liposomal therapy ex-vivo to induce apoptosis in CTC in blood. The TRAIL-based therapy killed approximately 75% of single CTCs and CTC in cluster form.

Conclusion: Collectively, these data indicate that CTC cluster and CAF levels can be used as a predictive biomarker for cancer recurrence. Moreover, for the first time, we demonstrate the efficacy of our TRAIL-based liposomal therapy to target and kill prostate CTC in primary patient blood samples, suggesting a potential new adjuvant therapy to use in combination with surgery.

Keywords: CAFs; CTC cluster; CTC mobilization; Cancer recurrence; Prostatectomy; TRAIL-liposomal therapy.

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Cancer-Associated Fibroblasts / immunology
  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology
  • Combined Modality Therapy
  • Cytotoxicity, Immunologic / drug effects*
  • Humans
  • Leukocytes / drug effects*
  • Leukocytes / immunology*
  • Leukocytes / metabolism
  • Liposomes
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / immunology*
  • Neoplastic Cells, Circulating / pathology
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Recurrence
  • TNF-Related Apoptosis-Inducing Ligand / administration & dosage
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Tumor Microenvironment / immunology


  • Biomarkers, Tumor
  • Liposomes
  • TNF-Related Apoptosis-Inducing Ligand