Theranostics 2016; 6(9):1453-1466. doi:10.7150/thno.14145

Research Paper

In Vivo Visualization of Tumor Antigen-containing Microparticles Generated in Fluorescent-protein-elicited Immunity

Fei Yang1,2*, Shun Liu1,2*, Xiuli Liu1,2*, Lei Liu1,2*, Meijie Luo1,2, Shuhong Qi1,2, Guoqiang Xu1,2, Sha Qiao1,2, Xiaohua Lv1,2, Xiangning Li1,2, Ling Fu1,2, Qingming Luo1,2✉, Zhihong Zhang1,2✉

1. Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan 430074, China;
2. MoE Key Laboratory for Biomedical Photonics, Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.
*These authors contributed equally to this work.

Abstract

In vivo optical spatio-temporal imaging of the tumor microenvironment is useful to explain how tumor immunotherapies work. However, the lack of fluorescent antigens with strong immunogenicity makes it difficult to study the dynamics of how tumors are eliminated by any given immune response. Here, we develop an effective fluorescent model antigen based on the tetrameric far-red fluorescent protein KatushkaS158A (tfRFP), which elicits both humoral and cellular immunity. We use this fluorescent antigen to visualize the dynamic behavior of immunocytes as they attack and selectively eliminate tfRFP-expressing tumors in vivo; swarms of immunocytes rush toward tumors with high motility, clusters of immunocytes form quickly, and numerous antigen-antibody complexes in the form of tfRFP+ microparticles are generated in the tumor areas and ingested by macrophages in the tumor microenvironment. Therefore, tfRFP, as both a model antigen and fluorescent reporter, is a useful tool to visualize specific immune responses in vivo.

Keywords: intravital imaging, fluorescent protein, immune response, microparticle, tumor immunology.

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How to cite this article:
Yang F, Liu S, Liu X, Liu L, Luo M, Qi S, Xu G, Qiao S, Lv X, Li X, Fu L, Luo Q, Zhang Z. In Vivo Visualization of Tumor Antigen-containing Microparticles Generated in Fluorescent-protein-elicited Immunity. Theranostics 2016; 6(9):1453-1466. doi:10.7150/thno.14145. Available from http://www.thno.org/v06p1453.htm