Anti-CD40-induced inflammatory E-cadherin+ dendritic cells enhance T cell responses and antitumour immunity in murine Lewis lung carcinoma

Journal of Experimental & Clinical Cancer Research

Li Liu³  Yan Wang⁵  Kunwu Yu⁴  Xiaohua Hong³  Yamei Zheng¹  Kai Zhang³  Kai Teng²  Yue Hu³  Xiaoyan Hu³  Yong Zhang³ 

[1] Department of oncology, Central Hospital of Wuhan, Wuhan, Hubei, China;Hainan Cancer Hospital, Haikou, Hainan, China;Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, 156 Wujiadun, Wuhan 430023, Hubei, China;Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China;Institute of Hydro Biololgy, Chinese Academy of Sciences, Analysis and Testing center, Wuhan, China

关键词: Activity;    Lung cancer;    T cell;    Dendritic cell;    E-cadherin;   

Others  :  1133391
DOI  :  10.1186/s13046-015-0126-9

 received in 2014-11-06, accepted in 2015-01-19,  发布年份 2015

【 摘 要 】

Background

Agonistic CD40 antibodies have been demonstrated to activate antigen-presenting cells (APCs) and enhance antitumour T cell responses, thereby providing a new therapeutic option in cancer immunotherapy. In agonistic CD40 antibody-mediated inflammatory responses, a novel subset of E-cadherin + dendritic cells (DCs) has been identified, and little is known about the role of these DCs in tumour immunity. This study investigated the effect of anti-CD40-mediated inflammatory E-cadherin + DCs in murine Lewis lung carcinoma (LLC).

Methods

The phenotype and characteristics of anti-CD40-mediated inflammatory E-cadherin + DCs isolated from the anti-CD40 model were assessed in vitro. The antitumour activity of E-cadherin + DCs were evaluated in vivo by promoting the differentiation of effector CD4+ T cells, CEA-specific CD8+ T cells and CD103+ CD8+ T cells and assessing their resistance to tumour challenge, including variations in tumour volume and survival curves.

Results

Here, we demonstrated that anti-CD40-mediated E-cadherin + inflammatory DCs accumulate in the lungs of Rag1 KO mice and were able to stimulate naïve CD4+ T cells to induce Th1 and Th17 cell differentiation and polarisation and to inhibit regulatory T cell and Th2 responses. Importantly, with the adoptive transfer of E-cadherin + DCs into the Lewis lung cancer model, the inflammatory DCs increased the Th1 and Th17 cell responses and reduced the Treg cell and Th2 responses. Interestingly, following the injection of inflammatory E-cadherin + DCs, the CD103+ CD8+ T cell and CEA-specific CD8+ T cell responses increased and exhibited potent antitumour immunity.

Conclusions

These findings indicate that anti-CD40-induced E-cadherin + DCs enhance T cell responses and antitumour activity in non-small cell lung cancer (NSCLC)-bearing mice and may be used to enhance the efficacy of DC-based peptide vaccines against NSCLC.

【 授权许可】

   
2015 Zhang et al.; licensee BioMed Central.

【 图 表 】

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