Co-immunization with L-Myc enhances CD8+ or CD103+ DCs mediated tumor-specific multi-functional CD8+ T cell responses

被引:10
|
作者
Chai, Dafei [1 ,2 ,3 ]
Zhang, Zichun [1 ,4 ]
Jiang, Nan [1 ,4 ]
Ding, Jiage [1 ,3 ]
Qiu, Dong [4 ]
Shi, Shang Yuchen [5 ]
Wang, Gang [1 ,2 ,3 ]
Fang, Lin [1 ,2 ,3 ]
Li, Huizhong [1 ,2 ,3 ]
Tian, Hui [1 ,2 ,3 ]
Yang, Jie [1 ,2 ,3 ]
Zhang, Qing [1 ,2 ,3 ]
Zheng, Junnian [2 ,3 ]
机构
[1] Xuzhou Med Univ, Canc Inst, 84 West Huaihai Rd, Xuzhou 221002, Jiangsu, Peoples R China
[2] Xuzhou Med Univ, Canc Inst, Jiangsu Ctr Collaborat & Innovat Canc Biotherapy, Xuzhou, Jiangsu, Peoples R China
[3] Xuzhou Med Univ, Ctr Clin Oncol, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China
[4] Xuzhou Med Univ, Dept Urol, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China
[5] Xuzhou Med Univ, Dept Radiat Oncol, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
CAIX; CS nanoparticles; L-Myc; multi-functional CD8(+) T cells; renal carcinoma; tumor vaccine; DNA VACCINE; DENDRITIC CELLS; IMMUNE-RESPONSE; CARCINOMA; CD4(+); G250; ANTIGEN; GENE; EXPRESSION; MARKER;
D O I
10.1111/cas.15044
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle-mediated DNA vaccine containing an activated factor L-Myc and a tumor-specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS-pL-Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS-pL-Myc/pCAIX co-immunization group. The increased proportion and mature of CD11c(+) DCs, CD8(+)CD11c(+) DCs and CD103(+)CD11c(+) DCs were observed in the splenocytes from CS-pL-Myc/pCAIX co-immunized mice. Furthermore, the enhanced antigen-specific CD8(+) T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi-functional CD8(+) T cell induction were detected in CS-pL-Myc/pCAIX co-immunization group compared with CS-pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8(+) T cells or CD8(+)CD11c(+) DCs and the loss of anti-tumor efficacy induced by CS-pL-Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8(+) DCs and CD103(+) DCs mediated CD8(+) T cells responses. Likewise, CS-pL-Myc/pCAIX co-immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi-functional CD8(+) T cell responses. Therefore, these results indicated that CS-pL-Myc/pCAIX vaccine could effectively induce CD8(+) DCs and CD103(+) DCs mediated tumor-specific multi-functional CD8(+) T cell responses and exert the anti-tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment.
引用
收藏
页码:3469 / 3483
页数:15
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