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Updated: Apr 15, 2026
Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
MicroRNA profiling of CD3+ CD56+ cytokine-induced killer cells
Wenju Wang1, Ruhong Li1, Mingyao Meng1
11] Yan'an Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan, People's Republic of China [2] Yunnan Cell Biology and Clinical Translation Research Center, Kunming 650051, Yunnan, People's Republic of China.
Abstract:
Studies have proven that IL-2 and IL-15 showed contrasting roles during CIK cells preparation. By employing microarray, we analyzed miRNA expression profiles of PBMC, CIKIL-2 and CIKIL-15. Advanced bioinformatic analyses were performed to explore the key miRNAs which may regulate cell proliferation and anti-tumor activity of CIK. We identified 261 differentially expressed miRNAs (DEMs) between PBMC and CIKIL-2, and 249 DEMs between PBMC and CIKIL-15. MiR-143-3p/miR-145-5p was miRNA cluster which may positively regulate cell proliferation. In contrast, miR-340-5p/miR-340-3p cluster may negatively regulate cell proliferation via induction apoptosis, which may cause decreased cell proliferation capacity of CIKIL-2. MiRNA-target interaction analysis indicated that 10 co-downregulated miRNAs may synergistically turn on the expression of a pool of tumor cytotoxic genes in CIK cells. The DEMs between CIKIL-2 and CIKIL-15 may contribute to enhanced tumor cytotoxic capacity of CIKIL-2. Importantly, we found that repressed miR-193a-5p may regulate the expressions of inhibitory receptor KLRD1. The results of the validation assay have shown that KLRD1 were upregulated in CIK cells. Our findings have provided new insights into mechanisms of CIK cells production and tumor cytotoxic function, and shed light on their safety for clinical trial.
Insights
Interleukin-2 (IL-2) and Interleukin-15 (IL-15) influence cytokine-induced killer (CIK) cell preparation differently. Microarray analysis revealed key microRNAs regulating CIK cell proliferation and anti-tumor activity, offering insights for clinical applications.
Area of Science:
- Immunology
- Molecular Biology
- Bioinformatics
Background:
- Interleukin-2 (IL-2) and Interleukin-15 (IL-15) play distinct roles in the preparation of cytokine-induced killer (CIK) cells.
- Understanding microRNA (miRNA) expression is crucial for optimizing CIK cell production and function.
Purpose of the Study:
- To analyze miRNA expression profiles in peripheral blood mononuclear cells (PBMC), CIK cells cultured with IL-2 (CIKIL-2), and CIK cells cultured with IL-15 (CIKIL-15).
- To identify key miRNAs regulating CIK cell proliferation and anti-tumor activity.
- To elucidate the role of specific miRNAs in CIK cell-mediated tumor cytotoxicity.
Main Methods:
- Microarray analysis to profile miRNA expression.
- Bioinformatic analyses for differential expression and target prediction.
- Validation assays to confirm miRNA and target gene expression.
Main Results:
- Identified 261 differentially expressed miRNAs (DEMs) between PBMC and CIKIL-2, and 249 DEMs between PBMC and CIKIL-15.
- Discovered miRNA clusters (e.g., miR-143-3p/miR-145-5p, miR-340-5p/miR-340-3p) influencing cell proliferation.
- Found that 10 co-downregulated miRNAs may enhance tumor cytotoxic genes, and repressed miR-193a-5p may regulate KLRD1 expression, which was upregulated in CIK cells.
Conclusions:
- miRNA expression profiles differ significantly based on IL-2 or IL-15 stimulation during CIK cell preparation.
- Specific miRNAs regulate CIK cell proliferation and anti-tumor functions, providing targets for optimization.
- Findings offer insights into CIK cell production mechanisms and tumoricidal capacity, supporting their potential for clinical trials.
