Journal
THERANOSTICS
Volume 6, Issue 9, Pages 1453-1466Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.14145
Keywords
intravital imaging; fluorescent protein; immune response; microparticle; tumor immunology
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Funding
- Major Research plan of the National Natural Science Foundation of China [91442201]
- Science Fund for Creative Research Group of China [61421064]
- Fundamental Research Funds for the Central Universities [HUST: 2015ZDTD014]
- WNLO
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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.
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