ArticlePloS one2018
Stimulation of natural killer cells with rhCD137 ligand enhances tumor-targeting antibody efficacy in gastric cancer.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Exosomal miR‑3681‑3p from M2‑polarized macrophages confers cisplatin resistance to gastric cancer cells by targeting MLH1.Molecular medicine reports · 2025Article
- CDH17 nanobodies facilitate rapid imaging of gastric cancer and efficient delivery of immunotoxin.Biomaterials research · 2022Article
- Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment.Nature reviews. Drug discovery · 2022Review
- The Road Less Taken: Less Appreciated Pathways for Manipulating CD8Frontiers in immunology · 2022Review
- The Right Partner in Crime: Unlocking the Potential of the Anti-EGFR Antibody CetuximabFrontiers in immunology · 2021Review
- Immune Cell Landscape in Gastric Cancer.BioMed research international · 2021Article
- Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors.Frontiers in cell and developmental biology · 2021Review
- Combination of CpG Oligodeoxynucleotide and Anti-4-1BB Antibody in the Treatment of Multiple Hepatocellular Carcinoma in Mice.OncoTargets and therapy · 2020Article
- The role of natural killer cells in hepatocellular carcinoma development and treatment: A narrative review.Translational oncology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although many anticancer agents for gastric cancer have been developed, the prognosis for many patients remains poor. Recently, costimulatory immune molecules that reactivate antitumor immune responses by utilizing the host immune system have attracted attention as new therapeutic strategies. CD137 is a costimulatory molecule that reportedly potentiates the antitumor activity of tumor-targeting monoclonal antibodies (mAbs) by enhancing antibody-dependent cellular cytotoxicity. However, it remains unclear whether CD137 stimulates tumor-regulatory activity in gastric cancer. In this study, we investigated the antitumor effects of CD137 stimulation on gastric cancer cells administered tumor-targeting mAbs. Our results showed that human natural killer (NK) cells were activated by expressing CD137 after encountering trastuzumab-coated gastric cancer cells, and that stimulation of activated NK cells in the presence of trastuzumab and recombinant human CD137 ligand (rhCD137L) enhanced cytotoxicity and release of cytokines (IFN-γ, TNF, granzyme A, or granzyme B) as compared with activated NK cells with trastuzumab alone (p < 0.05). By combination treatment with rhCD137L, similar effects were obtained regarding cancer cell cytotoxicity in the presence of cetuximab (p < 0.01). Moreover, we revealed that CD137 expression was dependent upon the affinity between the Fc portion of the antibodies and FcγRIIIa of NK cells based on results indicating that human IgG1 and IgG3 subclasses enhanced CD137 expression (p < 0.001). These results confirmed that FcγRIIIA polymorphisms (158 V/V) enhanced CD137 expression to a greater degree than 158 F polymorphisms (p = 0.014). Our results suggested that CD137 stimulation could promote the effects of tumor-targeting mAbs in gastric cancer, and that further investigation of antibody binding affinity and in vivo activities might improve therapeutic strategies related to the treatment of gastric cancer patients.
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