Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy

Qi, Shuhong; Li, Hui; Lu, Lisen; Qi, Zhongyang; Liu, Lei; Chen, Lu; Shen, Guanxin; Fu, Ling; Luo, Qingming; Zhang, Zhihong

doi:10.7554/elife.14756

Cited by 46 publications

(42 citation statements)

References 64 publications

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“…It was found that the combined system outperformed the single system, and it was suitable for quantitative three‐dimensional imaging of the fluophor . Furthermore, aiming at the significant demand for the visualization research of tumor immunity, they developed multiscale optical imaging approaches , optimized red‐shift fluorescent protein probes , established multicolor labeling animal models, and achieved the in vivo visualization of specific antitumor immune response and immunotherapy .…”

Section: Selected Research Achievementsmentioning

confidence: 99%

Biophotonics in China

Shi

Luo

2017

Journal of Biophotonics

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Biophotonics is a highly interdisciplinary field where physicists, chemists, biologists, physicians and engineers work together to solve the problems appearing in biology and medicine. In China, the Biophotonics discipline is often referred to as Biomedical Photonics, under the first‐level disciplines Biomedical Engineering or Optical Engineering, and was initiated in the late 1990s. Over the past 20 years, biophotonics research in China expanded extraordinarily and has reached the frontiers of the world‐level sciences. This white paper introduces the research groups in the biophotonics field in China, and their representative contributions.

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Section: Selected Research Achievementsmentioning

confidence: 99%

Biophotonics in China

Shi

Luo

2017

Journal of Biophotonics

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“…However, it is unclear how these two therapies synergize and no spatio‐temporal dynamics have been described in vivo. By imaging implanted melanoma tumors, Qi et al showed that regulatory T cells form an “immunosuppressive ring” around the solid tumor that prevents infiltration by the adoptive CTLs and other anticancer immune cells . Pretreatment with CTX before ATC not only led to the removal of the immunosuppressive barrier but also promoted the accumulation of adoptive CTLs and endogenous immune cells in the tumor area.…”

Section: Translational Potential Of Iv‐mpm For Cancermentioning

confidence: 99%

Frontiers in intravital multiphoton microscopy of cancer

2019

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Background Cancer is a highly complex disease, which involves the cooperation of tumor cells with multiple types of host cells and the extracellular matrix. Cancer studies that rely solely on static measurements of individual cell types are insufficient to dissect this complexity. In the last two decades, intravital microscopy has established itself as a powerful technique that can significantly improve our understanding of cancer by revealing the dynamic interactions governing cancer initiation, progression, and treatment effects in living animals. This review focuses on intravital multiphoton microscopy (IV‐MPM) applications in mouse models of cancer. Recent findings IV‐MPM studies have already enabled a deeper understanding of the complex events occurring in cancer at the molecular, cellular, and tissue levels. Multiple cell types present in different tissues influence cancer cell behavior via activation of distinct signaling pathways. As a result, the boundaries in the field of IV‐MPM are continuously being pushed to provide an integrated comprehension of cancer. We propose that optics, informatics, and cancer (cell) biology are coevolving as a new field. We have identified four emerging themes in this new field. First, new microscopy systems and image processing algorithms are enabling the simultaneous identification of multiple interactions between the tumor cells and the components of the tumor microenvironment. Second, techniques from molecular biology are being exploited to visualize subcellular structures and protein activities within individual cells of interest and relate those to phenotypic decisions, opening the door for “in vivo cell biology”. Third, combining IV‐MPM with additional imaging modalities or omics studies holds promise for linking the cell phenotype to its genotype, metabolic state, or tissue location. Finally, the clinical use of IV‐MPM for analyzing efficacy of anticancer treatments is steadily growing, suggesting a future role of IV‐MPM for personalized medicine. Conclusion IV‐MPM has revolutionized visualization of tumor‐microenvironment interactions in real time. Moving forward, incorporation of novel optics, automated image processing, and omics technologies in the study of cancer biology, will not only advance our understanding of the underlying complexities but will also leverage the unique aspects of IV‐MPM for clinical use.

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“…The vast majority of them, including DNA 8,9 -and RNA [10][11][12][13] -based PCR and reverse transcription quantitative real-time PCR (RT-qPCR), species-specific transcriptome [14][15][16][17][18][19][20] and proteome 21,22 analyses as well as flow cytometry [23][24][25] , are molecular profiling approaches which require tissue dissociation or lysis and do not address host contribution in situ on a single cell level. To investigate the unperturbed interaction between the tumor and its microenvironment, the use of genetically modified cells or mouse models expressing fluorescent reporter proteins [26][27][28][29][30] might want to be avoided. Others, inluding less common DNA [31][32][33] -and RNA 34,35 -in situ hybridization as well as broadly used IHC [36][37][38][39][40][41] , do address this aspect but harbor the limitations to be either difficult to evaluate and interpret, as this is the case for in situ hybridization approaches, or to rely on mouse-specific probes or antibodies which target only one particular cell type (Fig.…”

Section: Comparison With Existing Approachesmentioning

confidence: 99%

An antibody-based approach for the in situ evaluation of mouse contribution in human stem cell-derived xenografts

Hengstschläger¹,

Rosner²

2018

Protocol Exchange

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Studying human xenografts in mice is a widely used and powerful approach in both, stem cell and cancer research. Since the indispensible role of invaded host cells for teratoma respectively tumor development became evident, sensitive methods to detect mouse infiltration are in demand. For this purpose, in situ-labeling is generally preferred since it allows to draw valuable conclusions on host cell properties such as cell morphology, location and structural assembly. Unlike existing approaches, which employ species-specific antibodies to detect distinct cell types such as endothelial cells, immune cells or fibroblasts, our protocol exploits the species-specific detection of a proven housekeeping protein to visualize the microenvironment as a whole. So far undescribed, this 24-hours fluorescent immunohistochemistry (IHC) protocol enables the detection of mouse cells irrespective of a particular cell type or subpopulation and thus allows to draw are more comprehensive picture of host cell contribution in a single detection step.

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Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy

Cited by 46 publications

References 64 publications

Biophotonics in China

Biophotonics in China

Frontiers in intravital multiphoton microscopy of cancer

An antibody-based approach for the in situ evaluation of mouse contribution in human stem cell-derived xenografts

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