Intravital microscopy in the study of the tumor microenvironment: from bench to human application

Gabriel, Emmanuel; Fisher, Daniel; Evans, Sharon S.; Takabe, Kazuaki; Skitzki, Joseph J.

doi:10.18632/oncotarget.24957

Cited by 33 publications

(28 citation statements)

References 133 publications

(144 reference statements)

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“…We anticipate that this study will elucidate the structural and hemodynamic properties of vessels associated with solid tumors, building on previous studies that used IVM in human cancers [ 3 , 15 ]. In order to model the effects of tumor-associated vessel function on patient outcomes, direct examination of the microvasculature is essential and critical to be performed in humans.…”

Section: Discussionmentioning

confidence: 99%

Intravital Microscopy (IVM) in Human Solid Tumors: Novel Protocol to Examine Tumor-Associated Vessels

et al. 2020

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Background Intravital microscopy (IVM) allows the real-time, direct visualization of microscopic blood vessels. This pilot clinical trial will elucidate the physical and functional characteristics of vessels associated with solid tumors. Objective The main objective of this study is to determine the feasibility of performing IVM in patients with solid tumors during the standard course of surgical resection. IVM will also be performed when vasopressors or fluid boluses are administered during the standard course of the operation. Methods This is an open-label, nonrandomized, single-center, pilot study of IVM observation in subjects with solid tumors undergoing surgical resection. Results This study was active on January 1, 2019 (NCT03823144) and funded by the Mayo Clinic Florida Cancer Focused Research Team Award. As of September 27, 2020, we had enrolled 20 patients. Accrual period is expected to end by December 31, 2021. Conclusions This trial will support the development of interventions to improve patient treatment by extending the application of IVM to the tumor microenvironment. IVM observations during volume and pressor management at the time of surgery may aid in the development of strategies to augment responses to systemic treatments. International Registered Report Identifier (IRRID) PRR1-10.2196/15677

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Section: Discussionmentioning

confidence: 99%

Intravital Microscopy (IVM) in Human Solid Tumors: Novel Protocol to Examine Tumor-Associated Vessels

et al. 2020

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“…Most of the knowledge regarding vasculatures and drug/NP delivery in tumors was obtained from preclinical models. Recent advances in intravital highresolution imaging in tumors of human patients in the clinical setting reveal that 1) vessels are disorganized and tortuous, as observed in animal tumors; 2) ;50% of tumor vessels are not open; and 3) vessel diameters are larger and vessel wall shear stress is lower than predicted from immunohistochemistry or preclinical intravital microscopy results (Fisher et al, 2016;Gabriel et al, 2018).…”

Section: B Differences In Blood and Lymph Vasculatures In Normal Andmentioning

confidence: 99%

Target Site Delivery and Residence of Nanomedicines: Application of Quantitative Systems Pharmacology

Abbiati

Wientjes

et al. 2019

Pharmacol Rev

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“…The recent advances in near‐IR intravital microscopes (see section ), together with the development of novel label‐free imaging methods (see section ), have opened the door to IV‐MPM in cancer patients . For example, the DermInspect and MPTflex devices (JenLab) were used for melanoma detection in patients .…”

Section: Translational Potential Of Iv‐mpm For Cancermentioning

confidence: 99%

“…The recent advances in near-IR intravital microscopes (see section 2.1), together with the development of novel label-free imaging methods (see section 5.2), have opened the door to IV-MPM in cancer patients. [174][175][176][177][178][179] For example, the DermInspect and MPTflex devices (JenLab) were used for melanoma detection in patients. [177][178][179] Confocal laser endomicroscopy is used intravitally, in place of classical histology, for gastrointestinal and bladder urothelial tumors.…”

Section: Clinical Uses Of Iv-mpm Of 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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Intravital microscopy in the study of the tumor microenvironment: from bench to human application

Cited by 33 publications

References 133 publications

Intravital Microscopy (IVM) in Human Solid Tumors: Novel Protocol to Examine Tumor-Associated Vessels

Intravital Microscopy (IVM) in Human Solid Tumors: Novel Protocol to Examine Tumor-Associated Vessels

Target Site Delivery and Residence of Nanomedicines: Application of Quantitative Systems Pharmacology

Frontiers in intravital multiphoton microscopy of cancer

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