树突状细胞/肿瘤融合细胞疫苗诱导 CD4 T 细胞对肿瘤的消退作用。

Tumor regression by CD4 T-cells primed with dendritic/tumor fusion cell vaccines.

机构信息

Department of Internal Medicine, The Jikei University School of Medicine, Chiba, Japan

Department of Urology, Mitsui Memorial Hospital, Tokyo, Japan.

出版信息

Anticancer Res. 2014 Aug;34(8):3917-24.

Abstract

BACKGROUND/AIM: Vaccination with fusions of dendritic cells (DCs) and mucin-1 (MUC1)-positive tumor cells (FC/MUC1) induces MUC1-specific antitumor immunity. However, little is known about the function of Cluster of Differentiation (CD)4 T-cells primed with FC/MUC1 in MUC1 transgenic (MUC1.Tg) mice.

MATERIALS AND METHODS

CD4 T-cells primed with FC/MUC1 were analyzed by flow cytometry. Antitumor immunity by adoptive transfer of primed CD4 T-cells in Rag2(-/-) mice was assessed.

RESULTS

The effector and memory T-cells generated with FC/MUC1 were crucial to maintenance of long-term antitumor immunity. MUC1-8-mer peptide SAPDTRPA presented by FC/MUC1 was recognized by CD4 and CD8 T-cells. A subset of primed CD4 T-cells possessed cytotoxicity to lyse major histocompatibility complex (MHC) class I and MUC1 positive tumor cells. Interestingly, adoptive transfer of primed CD4 T-cells prevented lung metastasis in Rag2(-/-) mice.

CONCLUSION

CD4 T-cells primed by FC/MUC1 play direct role in antitumor immunity.

摘要

背景/目的：用树突状细胞（DC）和黏蛋白-1（MUC1）阳性肿瘤细胞融合物（FC/MUC1）进行疫苗接种可诱导 MUC1 特异性抗肿瘤免疫。然而，对于用 FC/MUC1 刺激的 CD4 T 细胞在 MUC1 转基因（MUC1.Tg）小鼠中的功能知之甚少。

材料和方法

通过流式细胞术分析用 FC/MUC1 刺激的 CD4 T 细胞。通过在 Rag2（-/-）小鼠中过继转移刺激的 CD4 T 细胞来评估抗肿瘤免疫。

结果

用 FC/MUC1 产生的效应和记忆 T 细胞对于维持长期抗肿瘤免疫至关重要。由 FC/MUC1 呈递的 MUC1-8 肽 SAPDTRPA 被 CD4 和 CD8 T 细胞识别。刺激的 CD4 T 细胞的一个亚群具有细胞毒性，可裂解主要组织相容性复合物（MHC）I 类和 MUC1 阳性肿瘤细胞。有趣的是，过继转移刺激的 CD4 T 细胞可预防 Rag2（-/-）小鼠的肺转移。