Reduction of major histocompatibility complex class I expression on bladder carcinoma following tumor antigen-pulsed dendritic cell vaccine: Implications for immunoresistance in therapy.
OBJECTIVE
To clarify the relationship between a decreased major histocompatibility complex class I (MHC-I) expression on bladder tumors and decreased immunological efficacy of tumor antigen-pulsed dendritic cell vaccine in a rat bladder carcinoma model induced by N-methyl-N-nitrosourea irrigation.


METHODS
Enzyme-linked immunosorbent assay was used to evaluate interferon-gamma concentration in the serum and colorimetric lactate dehydrogenase release assay in vitro was used to test the cytotoxicity capability of T lymphocytes. MHC-I expression on tumor cells was detected by flow cytometry and analyzed with CellQuest software.


RESULTS
The tumor antigen sensitized dendritic cell vaccine group showed decreased hyperplastic formations, lower pathological stages in rat bladders and more potent cytotoxicity activity (P < 0.001) than the dendritic cell vaccine group. Additionally, immunization with pulsed dendritic cell vaccine induced higher specific cytokine production of interferon-gamma. Nevertheless, a decreased MHC-I expression on bladder tumors was tested after immunotherapy by pulsed dendritic cell vaccine on week 15. As expected, the cytotoxic activity of T lymphocytes from rats on tumor cells with low MHC-I expression was also decreased to 19.70 +/- 4.82% as compared with tumor cells with high MHC-I (52.10 +/- 8.66%, P = 0.005).


CONCLUSIONS
Tumor antigen sensitized dendritic cell vaccine has beneficial activity on N-methyl-N-nitrosourea-induced bladder cancer in situ in rats, but therapeutic responses are accompanied by decreased MHC-I expression on tumors, possibly suggesting poor long-term therapeutic outcomes.
Li
Mengqiang
M
Department of Urology, the Affiliated Union Hospital of Fujian Medical University, Fuzhou, China. limengqiang1976@163.com
Wang
Huili
H
Xi
Zhijun
Z
Xu
Enci
E
Jiang
Xuejun
X
Chen
Jiangying
J
Shi
Wenzhen
W
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology*
D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I