Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy
- Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, China
- Tongji Medical College, China
Abstract
The combined-immunotherapy of adoptive cell therapy (ACT) and cyclophosphamide (CTX) is one of the most efficient treatments for melanoma patients. However, synergistic effects of CTX and ACT on the spatio-temporal dynamics of immunocytes in vivo have not been described. Here, we visualized key cell events of immunotherapy-elicited immunoreactions in a multicolor-coded tumor microenvironment, and then established an optimal strategy of metronomic combined-immunotherapy to enhance anti-tumor efficacy. Intravital imaging data indicated that regulatory T cells formed an 'immunosuppressive ring' around a solid tumor. The CTX-ACT combined-treatment elicited synergistic immunoreactions in tumor areas, which included relieving the immune suppression, triggering the transient activation of endogenous tumor-infiltrating immunocytes, increasing the accumulation of adoptive cytotoxic T lymphocytes, and accelerating the infiltration of dendritic cells. These insights into the spatio-temporal dynamics of immunocytes are beneficial for optimizing immunotherapy and provide new approaches for elucidating the mechanisms underlying the involvement of immunocytes in cancer immunotherapy.
Article and author information
Author details
Funding
National Natural Science Foundation of China (91442201)
- Shuhong Qi
- Lisen Lu
- Lei Liu
- Zhihong Zhang
Ministry of Science and Technology of the People's Republic of China (2011CB910401)
- Shuhong Qi
- Hui Li
- Lei Liu
- Qingming Luo
- Zhihong Zhang
National Natural Science Foundation of China (61421064)
- Ling Fu
- Qingming Luo
- Zhihong Zhang
Ministry of Education of the People's Republic of China (2015ZDTD014)
- Shuhong Qi
- Lisen Lu
- Lei Liu
- Zhihong Zhang
Ministry of Science and Technology of the People's Republic of China (Director fund of Wuhan National Laboratory for Optoelectronics)
- Shuhong Qi
- Lisen Lu
- Lei Liu
- Qingming Luo
- Zhihong Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Xuetao Cao, Zhejiang University School of Medicine, China
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Hubei Provincial Animal Care and Use Committee. The protocol was approved by the Animal Experimentation Ethics Committee of Huazhong University of Science and Technology (reference number: 452). All surgery was performed under ketamine and xylazine, and all intravital imaging experiments were performed under 1-3 % isoflurane in oxygen, every effort was made to minimize suffering.
Version history
- Received: January 28, 2016
- Accepted: October 17, 2016
- Accepted Manuscript published: November 18, 2016 (version 1)
- Version of Record published: December 20, 2016 (version 2)
Copyright
© 2016, Qi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy
eLife 5:e14756.
https://doi.org/10.7554/eLife.14756
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