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目的探讨荷瘤小鼠5-氟尿嘧啶治疗后,机体细胞免疫应答的改变及初步机制,为化疗结合免疫治疗提供理论依据。方法皮下注射Lewis肺癌细胞,不同时相点观察肿瘤大小的变化,流式细胞仪检测脾脏髓源抑制细胞(myeloid derived suppressor cell,MDSC)及CD8+T细胞的比例;尾静脉感染李斯特菌,胞内细胞因子染色检测抗原特异性CD8+T细胞免疫应答;标记CFSE的OT-I细胞过继转移实验,观察体内抗原特异性CD8+T细胞增殖。结果 5-氟尿嘧啶处理的荷瘤小鼠,肿瘤生长显著受到抑制;MDSC细胞的比例显著减少;机体总CD8+T细胞的比例没有明显的改变,感染李斯特菌感染后,5-氟尿嘧啶处理组,抗原特异性CD8+T细胞显著增多;抗原特异性CD8+T细胞体内增殖速率明显增强。结论荷瘤小鼠5-氟尿嘧啶治疗后,可以显著抑制MDSC,提高机体CD8+T细胞免疫应答。
Objective To investigate the changes and primary mechanism of cellular immune response after the treatment of 5-fluorouracil in tumor-bearing mice and to provide a theoretical basis for chemotherapy and immunotherapy. Methods Lewis lung carcinoma cells were injected subcutaneously and the tumor size was observed at different time points. The proportion of myeloid derived suppressor cells (MDSC) and CD8 + T cells in spleen was detected by flow cytometry. Listeria monocytogenes Antigen-specific CD8 + T cell immune response was detected by intracellular cytokine staining. The adoptive transfer assay of CFSE-labeled OT-I cells was used to observe the proliferation of antigen-specific CD8 + T cells in vivo. Results 5-Fluorouracil-treated tumor-bearing mice significantly inhibited tumor growth; the proportion of MDSC cells was significantly reduced; the proportion of total CD8 + T cells did not change significantly. After infection with Listeria monocytogenes, Antigen-specific CD8 + T cells were significantly increased; antigen-specific CD8 + T cell proliferation rate was significantly enhanced. Conclusion The treatment of 5-fluorouracil in tumor-bearing mice can significantly inhibit MDSC and enhance the immune response of CD8 + T cells.