Quantifying and visualising the nuances of cellular dynamics in vivo using intravital imaging

Murphy, Kendelle J.; Reed, Daniel A; Trpceski, Michael; Herrmann, David; Timpson, Paul

doi:10.1016/j.ceb.2021.04.007

Cited by 8 publications

(7 citation statements)

References 179 publications

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“…Spatial protein techniques, including multiplex immunohistochemistry (mIHC), multiplex immunofluorescence (mIF), cytometry by time of flight (CyTOF), and multiplex digital spatial profiling (DSP), allow for the simultaneous assessment of multiple protein markers and contribute to the acquisition of a more comprehensive microenvironment map [ 258 ]. Live or intravital imaging techniques, such as confocal microscopy, two-photon microscopy, and fluorescence-based biosensors, have shown attractive potential in subcellular dynamic tracking [ 259 , 260 ], allowing 3D monitoring and visualisation of NK cell interactions in the TME.…”

Section: Outlooks and Directionsmentioning

confidence: 99%

NK cells are never alone: crosstalk and communication in tumour microenvironments

Zhou

Lu²,

Liu

et al. 2023

Mol Cancer

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Immune escape is a hallmark of cancer. The dynamic and heterogeneous tumour microenvironment (TME) causes insufficient infiltration and poor efficacy of natural killer (NK) cell-based immunotherapy, which becomes a key factor triggering tumour progression. Understanding the crosstalk between NK cells and the TME provides new insights for optimising NK cell-based immunotherapy. Here, we present new advances in direct or indirect crosstalk between NK cells and 9 specialised TMEs, including immune, metabolic, innervated niche, mechanical, and microbial microenvironments, summarise TME-mediated mechanisms of NK cell function inhibition, and highlight potential targeted therapies for NK-TME crosstalk. Importantly, we discuss novel strategies to overcome the inhibitory TME and provide an attractive outlook for the future.

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Section: Outlooks and Directionsmentioning

confidence: 99%

NK cells are never alone: crosstalk and communication in tumour microenvironments

Zhou

Lu²,

Liu

et al. 2023

Mol Cancer

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“…In particular, transient or short-term manipulation of the stroma can deprive cancer cells of their supportive niche, whilst also minimising the likelihood of drug resistance and toxicity, which are often associated with long-term chronic treatments. In this context, intravital imaging and the live tracking of cancer cells can help optimise the efficacy of combination treatment schedules prior to long-term studies [ 107–109 ]. Beyond this, dual or companion biomarkers may facilitate the identification of patient subsets that are highly likely to respond to anti-fibrotic therapy in combination with other treatment approaches.…”

Section: Future Directionsmentioning

confidence: 99%

Focal adhesion kinase priming in pancreatic cancer, altering biomechanics to improve chemotherapy

Murphy

Zhu

Trpceski

et al. 2022

Biochemical Society Transactions

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The dense desmoplastic and fibrotic stroma is a characteristic feature of pancreatic ductal adenocarcinoma (PDAC), regulating disease progression, metastasis and response to treatment. Reciprocal interactions between the tumour and stroma are mediated by bidirectional integrin-mediated signalling, in particular by Focal Adhesion Kinase (FAK). FAK is often hyperactivated and overexpressed in aggressive cancers, promoting stromal remodelling and inducing tissue stiffness which can accelerate cancer cell proliferation, survival and chemoresistance. Therapeutic targeting of the PDAC stroma is an evolving area of interest for pre-clinical and clinical research, where a subtle reshaping of the stromal architecture prior to chemotherapy may prove promising in the clinical management of disease and overall patient survival. Here, we describe how transient stromal manipulation (or ‘priming’) via short-term FAK inhibition, rather than chronic treatment, can render PDAC cells exquisitely vulnerable to subsequent standard-of-care chemotherapy. We assess how our priming publication fits with the recent literature and describe in this perspective how this could impact future cancer treatment. This highlights the significance of treatment timing and warrants further consideration of anti-fibrotic therapies in the clinical management of PDAC and other fibrotic diseases.

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“…Genetically encoded fluorescent reporters and cell dyes generally need to be very bright to facilitate efficient excitation and fluorescence in deep tissues. Timpson and colleagues 63 recently reviewed many available genetic reporters for intravital imaging and different imaging modalities. T cells have long been shown to round up, decrease motility and increase calcium signaling upon interactions with antigen presenting cells 64,65 .…”

Section: Limitations For Quantitative Measurements Of Intravital Imag...mentioning

confidence: 99%

“…While HMMs are theoretically useful, they might require more information than velocity and angle from a single stained cell population 94 . Given the vast availability of cellular reporters for intravital imaging 63 it will be important to measure general cellular properties such as the shape of the cell, the intracellular actin cytoskeleton, the cell membrane, the nucleus or calcium signaling. This was useful for the CellProfiler community to measure many different cellular parameters in high throughput imaging studies to study the effect of different drug combinations, termed cell‐painting 95 .…”

Section: Approaches For Quantifying Immune Cell Behaviormentioning

confidence: 99%

Moving beyond velocity: Opportunities and challenges to quantify immune cell behavior*

Schienstock

Mueller

2021

Immunological Reviews

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The analysis of cellular behavior using intravital multi‐photon microscopy has contributed substantially to our understanding of the priming and effector phases of immune responses. Yet, many questions remain unanswered and unexplored. Though advancements in intravital imaging techniques and animal models continue to drive new discoveries, continued improvements in analysis methods are needed to extract detailed information about cellular behavior. Focusing on dendritic cell (DC) and T cell interactions as an exemplar, here we discuss key limitations for intravital imaging studies and review and explore alternative approaches to quantify immune cell behavior. We touch upon current developments in deep learning models, as well as established methods from unrelated fields such as ecology to detect and track objects over time. As developments in open‐source software make it possible to process and interactively view larger datasets, the challenge for the field will be to determine how best to combine intravital imaging with multi‐parameter imaging of larger tissue regions to discover new facets of leukocyte dynamics and how these contribute to immune responses.

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Quantifying and visualising the nuances of cellular dynamics in vivo using intravital imaging

Cited by 8 publications

References 179 publications

NK cells are never alone: crosstalk and communication in tumour microenvironments

NK cells are never alone: crosstalk and communication in tumour microenvironments

Focal adhesion kinase priming in pancreatic cancer, altering biomechanics to improve chemotherapy

Moving beyond velocity: Opportunities and challenges to quantify immune cell behavior*

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