Related Experiment Video
Updated: Nov 23, 2025
Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Targeting CD155 by rediocide-A overcomes tumour immuno-resistance to natural killer cells
Wanyi Ng1, Chenyuan Gong1,2, Xuewei Yan1
1Laboratory of Integrative Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
Context:
Therapeutic benefits of immunotherapy are restricted by cancer immune-resistance mechanisms. Rediocide-A (Red-A), a natural product extracted from Traditional Chinese Medicine, is a promising agent to battle against cancer which acts as an immune checkpoint inhibitor.
Objective:
To investigate the effect of Red-A on NK-cell tumouricidal activity.
Materials And Methods:
NK cells were co-cultured with A549 or H1299 cells and treated with 10 or 100 nM Red-A for 24 h. Cells treated with 0.1% dimethyl sulphoxide (DMSO) was employed as vehicle control. NK cell-mediated cytotoxicity was detected by biophotonic cytotoxicity and impedance assay. Degranulation, granzyme B, NK cell-tumour cell conjugates and ligands profiling were detected by flow cytometry. Interferon-γ (IFN- γ) production was assessed by enzyme-linked immunosorbent assay (ELISA).
Results:
Red-A increased NK cell-mediated lysis of A549 cells by 3.58-fold (21.86% vs. 78.27%) and H1299 cells by 1.26-fold (59.18% vs. 74.78%), compared to vehicle control. Granzyme B level was increased by 48.01% (A549 cells) and 53.26% (H1299 cells) after 100 nM Red-A treatment. INF-γ level was increased by 3.23-fold (A549 cells) and 6.77-fold (H1299 cells) after 100 nM Red-A treatment. Red-A treatment down-regulated the expression level of CD155 by 14.41% and 11.66% in A549 cells and H1299 cells, respectively, leading to the blockade of tumour immuno-resistance to NK cells.
Conclusions:
Red-A overcomes immuno-resistance of NSCLCs to NK cells by down-regulating CD155 expression, which shows the possibility of developing checkpoint inhibitors targeting TIGIT/CD155 signalling to overcome immuno-resistance of cancer cells.
Insights
Rediocide-A (Red-A) enhances natural killer (NK) cell activity against cancer by inhibiting immune resistance. This immune checkpoint inhibitor shows promise in overcoming tumor defenses by down-regulating CD155 expression.
Area of Science:
- Immunology
- Cancer Biology
- Pharmacology
Background:
- Cancer immunotherapy faces challenges due to immune resistance mechanisms.
- Rediocide-A (Red-A), a natural product from Traditional Chinese Medicine, acts as an immune checkpoint inhibitor.
- Red-A demonstrates potential in combating cancer by modulating immune responses.
Purpose of the Study:
- To evaluate the impact of Red-A on the tumor-killing activity of natural killer (NK) cells.
- To investigate Red-A's mechanism in overcoming cancer immune resistance.
Main Methods:
- NK cells were co-cultured with NSCLC cell lines (A549, H1299) and treated with Red-A.
- NK cell cytotoxicity, degranulation, granzyme B, and cytokine production (IFN-γ) were measured.
- Expression of CD155, a key ligand, was analyzed using flow cytometry.
Main Results:
- Red-A significantly increased NK cell-mediated lysis of A549 and H1299 cells.
- Treatment with Red-A elevated granzyme B and interferon-γ (IFN-γ) levels.
- Red-A down-regulated CD155 expression on cancer cells, suggesting a mechanism to overcome immune evasion.
Conclusions:
- Red-A enhances NK cell anti-tumor activity by reducing CD155 expression, thereby overcoming non-small cell lung cancer (NSCLC) immune resistance.
- Targeting the TIGIT/CD155 pathway with agents like Red-A offers a potential strategy to combat cancer immune evasion.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:27Tumor Immunotherapy
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
02:56Treatment Resistant Cancers