Objective       To investigate the mechanisms and significance of the histone deacetylase (HDAC) inhibitor in the enhancement of cellular immunotherapeutic efficiency for pancreatic cancer.       Methods       Pancreatic cancer cell lines PANC-1

BXPC-3 and CFPAC-1 were respectively treated with HDAC inhibitor

trichostatin A (TSA) at 50

100

200 and 400 μmol/L for 24 h. The cells without any treatment served as normal control. The expression of membrane type MICA/B was measured in above cells with flow cytometry

immunofluorescence staining and Western blotting. Then the cells were treated by the optimal concentration of 200 μmol/L TSA for 12

24

36 and 48 h to screen out the best treatment duration. When the dose of TSA was 200 nmol/L and treatment duration was 24 h

the expression of MICA/B was the highest. When the ratio of cytokine-induced killer (CIK) cells to the pancreatic cancer cells was 10∶1

the killing rate of CIK cells for the cells treated with TSA or not was measured by LDH release assay. Bivariate correlation analysis was used to study the relationship of killing rate of CIK cells and MICA/B expression.       Results       Flow cytometry showed that the expression rate of MICA/B was 2.2%

61.2% and 31.2% in PANC-1

BXPC-3 and  CFPAC-1 cells respectively. However

after the cells were treated by 200 nmol/L TSA for 24 h

the rate was 13.8%

86.6% and 76.1%

respectively

significantly higher than in the cells without treatment (P0.01). Moreover

immunofluorescence staining indicated that the cells were more strongly stained

and Western blotting found the the membrane protein MICA/B expression was enhanced in the pancreatic cancer cell lines after TSA treatment. With the ratio of 10∶1

the killing rate of CIK cells was 7.66%

12.03% and 12.15% respectively for PANC-1

BXPC-3 and CFPAC-1 cells

and the rates were 24.32%

58.63% and 49.25% respectively for the cells treated with 200 nmol/L TSA for 24 h (P0.01). The correlation coefficient were 0.959

0.964

0.972 respectively for the killing rates of CIK cells to PANC-1

BXPC-3

CFPAC-1 cells and the expression of MICA/B (P0.01)

indicating a positive correlation between the killing rates and the expression levels.       Conclusion       HDAC inhibitor can enhance CIK cells’ killing effect through increasing the MICA/B expression in pancreatic cancer cell lines

and thus improve the effect the cellular immunotherapy for pancreatic cancer.