Gemcitabine chemotherapy combined with intratumoral injection of dendritic cells in treatment of mouse large lymphoma
10.3872/j.issn.1007-385X.2009.06.002
- VernacularTitle:吉西他滨化疗联合树突状细胞瘤内注射对小鼠巨大淋巴瘤的治疗作用
- Author:
Shouyou HU
;
Xuejun ZHU
;
Zhenfang FAN
;
Xiangtu KONG
;
Yuchao CHEN
;
Jianyi CHEN
;
Jianmin JI
;
Xuemei SUN
- Publication Type:Journal Article
- Keywords:
lymphoma;
gemcitabine;
myeloid derived suppressor cell;
dendritic cell;
chemotherapy-immunotherapy
- From:
Chinese Journal of Cancer Biotherapy
2009;16(6):557-563
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of gemcitabine on myeloid derived suppressor cells (MDSC) in the spleen of B lymphoma cell-bearing mice, and the therapeutic effect of gemcitabine combined with intratumoral injection of dendritic cells (DCs) in treatment of large B lymphoma. Methods: BALB/c mice were inoculated subcutaneously with B lymphoma A20 cells; large tumors were formed 30 d after inoculation. Gr-1~+ CD11b~+ MDSC proportion in the spleen was analyzed by flow cytometry before and after gemcitabine treatment. Splenic MDSC sorted by immunomagnetic beads was further treated with gemcitabine, and then the apoptosis of MDSC was examined by Annexin-V/PI staining. Tumor growth and survival time of A20 tumor-bearing mice were observed after treatment with gemcitabine and intratumoral injection of DCs. Results: Splenic Gr-1~+ CD11b~+ MDSC ratio in A20 cell-bearing mice was 10 times higher than that in the normal mice. Gemcitabine induced apoptosis and necrosis of purified MDSC in vitro in a time-dependent manner. The percentage of MDSC in the spleen of A20 tumor-bearing mice was decreased after injection of a single dose of gemcitabine. Gemcit-abine or intratumoral injection of DCs alone inhibited growth of tumor to a certain degree, with the mean survival periods of mice in the gemcitabine, DCs, and untreated groups being (48.8±3.6) d, (47.2±7.4) d, and (38.8±2.2) d, respectively. Gemcitabine chemotherapy combined with intratumoral DC injection resulted in continuous shrink of the tumors, and 60% of the mice survived for more than 90 d. Conclusion: Gemcitabine can effectively eliminate splenic MDSC in tumor-bearing mice. Gemcitabine chemotherapy and DCs immunotherapy can work synergistically in the treat-ment of huge lymphoma. These results provide an experimental basis for the comprehensive chemotherapy and immunotber-apy of relapsed or refractory lymphoma.
