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Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
Intracellular poly(I:C) initiated gastric adenocarcinoma cell apoptosis and subsequently ameliorated NK cell
Jing Qu1, Zhaohua Hou, Qiuju Han
1Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Institute of Immunopharmacology and Immunotherapy, Shandong University , Jinan, China .
Abstract:
Natural killer (NK) cells are granular lymphocytic cells that exert essential functions in viral infection defense and tumor immune surveillance. However, the functions of NK cells were impaired in cancer patients. Polycytidylic acid [poly(I:C)] has been used as an immune adjuvant to improve innate and adaptive immune responses. In this study, intracellular poly(I:C) could trigger gastric adenocarcinoma cells apoptosis quickly. Meanwhile, the sensitivity of poly(I:C)-treated gastric adenocarcinoma cells to NK cell cytolysis was increased, concomitant with the elevated expression of MICA/B and Fas. Furthermore, the cytolytic activity of NK cells against tumor cells was augmented significantly by the supernatant from poly(I:C)-transfected tumor cells compared with NK cells treated by the supernatant from untreated tumor cells, as well as the proliferation and migration abilities of NK cells. In this process, the activating receptors and cytolysis-associated molecules of NK cells were up-regulated. Further investigation showed that type I interferon (IFN) produced by poly(I:C)-transfected gastric adenocarcinoma cells played an important role in this process. Our findings demonstrated that intracellular poly(I:C) not only triggered gastric adenocarcinoma cell apoptosis, but also enhanced NK responses via inducing type I IFN production by gastric adenocarcinoma cells. These functions make poly(I:C) a promising therapeutic medicine for gastric adenocarcinoma.
Insights
Intracellular polycytidylic acid [poly(I:C)] induces gastric cancer cell apoptosis and enhances natural killer (NK) cell anti-tumor activity. This immune stimulation, mediated by type I interferon, suggests poly(I:C) as a potential therapy for gastric adenocarcinoma.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Natural killer (NK) cells are crucial for anti-viral defense and tumor immune surveillance.
- NK cell function is often impaired in cancer patients.
- Polycytidylic acid [poly(I:C)] is an immune adjuvant known to enhance immune responses.
Purpose of the Study:
- To investigate the effects of intracellular poly(I:C) on gastric adenocarcinoma cells and NK cell activity.
- To explore the potential of poly(I:C) as a therapeutic agent for gastric cancer.
Main Methods:
- Gastric adenocarcinoma cells were treated with intracellular poly(I:C).
- Apoptosis, MICA/B and Fas expression, and NK cell-mediated cytotoxicity were assessed.
- Supernatants from poly(I:C)-treated cells were used to evaluate effects on NK cell proliferation, migration, and activity.
- Type I interferon (IFN) production was analyzed.
Main Results:
- Intracellular poly(I:C) rapidly induced apoptosis in gastric adenocarcinoma cells.
- Poly(I:C) treatment increased cancer cell sensitivity to NK cell-mediated lysis by upregulating MICA/B and Fas.
- Supernatants from poly(I:C)-treated cells significantly enhanced NK cell cytolytic activity, proliferation, and migration.
- Type I IFN produced by treated cancer cells was identified as a key mediator.
Conclusions:
- Intracellular poly(I:C) triggers gastric adenocarcinoma cell apoptosis and enhances NK cell responses.
- Poly(I:C) boosts NK cell activity by inducing type I IFN production from cancer cells.
- Poly(I:C) shows promise as a therapeutic agent for gastric adenocarcinoma.
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