KEY TAKEAWAYS
- The study aimed to investigate how esophageal CSCs evade NK cell cytotoxicity via ULBP-1 downregulation.
- Researchers found that esophageal CSCs evade NK cells by downregulating ULBP-1, suggesting a target for improved therapies.
Cancer stem-like cells (CSCs) are pivotal in the initiation and progression of aggressive cancers, including esophageal cancer, contributing to treatment resistance and tumor recurrence. Natural killer (NK) cells, vital components of innate immunity, can target and destroy various cancer cells, including CSCs, positioning NK cell-based therapy as a potential strategy to combat these resistant cells.
Bo Tang and the team aimed to examine the sensitivity of human esophageal CSCs to NK cell-mediated cytotoxicity, with a focus on understanding how these cells evade NK cell attacks.
They performed an inclusive analysis on CSCs enriched from human esophageal squamous cell carcinoma cell lines using sphere formation culture. Human NK cells were selectively expanded from the peripheral blood of healthy donors. Patients were assessed to understand the underlying mechanisms. qRT-PCR, flow cytometry, and ELISA assays were utilized to examine RNA expression and protein levels.
To evaluate the cytotoxicity of NK cells, CFSE-labeled target cells were co-cultured with human-activated NK cells, and flow cytometry was employed to detect and measure the extent of NK cell-mediated cytotoxicity.
About the results, researchers observed that esophageal CSCs were more resistant to NK cell-mediated cytotoxicity compared with their adherent counterparts. Consistently, esophageal CSCs exhibited down-regulated expression of ULBP-1, a ligand for the NK cell stimulatory receptor NKG2D. Knockdown of ULBP-1 led to significant inhibition of NK cell cytotoxicity against esophageal CSCs, while ULBP-1 overexpression resulted in the opposite effect.
Additionally, the pro-differentiation agent all-trans retinoic acid was found to enhance the sensitivity of esophageal CSCs to NK cell cytotoxicity.
The study concluded that esophageal CSCs exhibit increased resistance to NK cells due to the down-regulation of ULBP-1. This finding highlights a potential approach to enhance NK cell activity against esophageal CSCs, offering insights for developing more effective NK cell-based therapies.
This study was funded by the National Natural Science Foundation of China (82172704, 81773045) and the Medical Science and Technology Key Project of Henan Province, China (SBGJ202302038).
Source: https://pubmed.ncbi.nlm.nih.gov/39103915/
Tang B, Guo M, Zhai Y, et al. (2024). “Human esophageal cancer stem-like cells escape the cytotoxicity of natural killer cells via down-regulation of ULBP-1.” J Transl Med. 2024;22(1):737. Published 2024 Aug 5. doi:10.1186/s12967-024-05549-1
