IL-27 in combination with IL-15 regulates anti-tumor effect of NK92 cells by phosphorylating the STATs pathway
DOI：10.3872/j.issn.1007-385x.2021.03.007
- VernacularTitle:IL-27联合IL-15通过磷酸化STATs途径调控NK92细胞的抗肿瘤作用
- Author:
JIANG Yanan1,
1
;
SUN Yufei1
1
;
WANG Kun2,
2
;
FU Qiang1, 2, 3
3
,
4
,
5
Author Information
1. Department of Immunology, Binzhou Medical University, Yantai 264003, Shandong, China
2. Department of Biological Pharmacy, Binzhou Medical University, Yantai 264003, Shandong, China
3. Department of Immunology, Binzhou Medical University, Yantai 264003, Shandong, China;
4. Department of Biological Pharmacy, Binzhou Medical University, Yantai 264003, Shandong, China;
5. Shandong Cellogene Pharmaceutics Co., LTD., Yantai 264003, Shandong, China
- Publication Type:Journal Article
- Keywords:
IL-27;
IL-15;
NK92 cell;
Anti-tumor;
JAK-STAT pathway
- From:
Chinese Journal of Cancer Biotherapy
2021;28(3):261-268
- CountryChina
- Language:Chinese
-
Abstract:
[Abstract] Objective: To investigate the effect of IL-27 in combination with IL-15 on the anti-tumor effects of NK92 cells and the possible molecular and signaling mechanisms. Methods: NK92 cells with high IL-15 expression (IL-15-NK92 cells) were cultured in different mass concentrations of IL-27 (0, 10, 20, 30 and 60 ng/ml) for 24 h. The effects of IL-27 on IL-15 secretion, migration and proliferation of IL-15-NK92 cells were detected by ELISA, Transwell and CCK-8 assay, respectively. Flow cytometry was used to detect the expression levels of IL-15-NK92 cell surface receptors NKG2D, NKp30 and NKp46, as well as the secretion levels of perforin and granzyme B. LDH method was used to detect the cytotoxic effect of IL-15-NK92 cells on hematologic tumor cells and solid tumor cells, and WB was used to detect the expressions and phosphorylation level of STATs pathway-related proteins. Results: IL-27 at the concentration of 30 ng/ml promoted IL-15-NK92 cells secreting IL-15 (P<0.01), significantly enhanced the cell migration (P<0.05) but inhibited the proliferation of IL-15-NK92 cells (P<0.05). 30 ng/ml IL-27 could significantly promote the expressions of NKG2D, NKp30 and NKp46 on surface of IL-15-NK 92 cells, as well as elevate the secretion of perforin (all P<0.05), but didn’t affect the secretion of granzyme B (P>0.05); moreover, it also significantly enhanced the cytotoxicity of IL-15-NK92 cells against hematologic malignancies and solid tumor cells (P<0.05 or P<0.01), and up-regulated the phosphorylation levels of STAT1, STAT3 and STAT5 (all P<0.01). Conclusion: IL-27 can enhance the cytotoxicity of IL-15-NK92 cells against hematologic tumor cells and solid tumor cells, which might be related with its upregulation of phosphorylation level of STAT1, STAT3 and STAT5 in JAK-STAT pathway and multiple activating receptors in IL-15-NK92 cells.
- Full text:20210307.pdf
