Intravital Imaging of Adoptive T-Cell Morphology, Mobility and Trafficking Following Immune Checkpoint Inhibition in a Mouse Melanoma Model

Lau, Doreen; Garçon, Fabien; Chandra, Anita; Lechermann, Laura M.; Aloj, Luigi; Chilvers, Edwin R.; Corrie, Pippa; Okkenhaug, Klaus; Gallagher, Ferdia A.

doi:10.3389/fimmu.2020.01514

Cited by 29 publications

(25 citation statements)

References 59 publications

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“…As observed in other models and discussed above, in these untreated murine tumor models T cells exhibited greater motility in the tumor periphery than in the tumor core (199). Following PDL1 blockade alone or combined PDL1 and CTLA4 blockade T cell motility was decreased in all regions of the tumor and overall infiltration was increased (199), consistent with increased cognate interactions in the tumor environment.…”

Section: Effect Of Checkpoint Regulators On Retentionsupporting

confidence: 74%

“…However, the frequency of these populations in the blood did not correlate well with their proportions in the tumor. Lau et al demonstrated that combined PDL1 and CTLA4 blockade resulted in increased overall numbers of antigen-experienced T cells in murine tumors, and that these cells were more heterogeneously distributed than in untreated tumors (199). As observed in other models and discussed above, in these untreated murine tumor models T cells exhibited greater motility in the tumor periphery than in the tumor core (199).…”

Section: Effect Of Checkpoint Regulators On Retentionmentioning

confidence: 88%

“…Lau et al demonstrated that combined PDL1 and CTLA4 blockade resulted in increased overall numbers of antigen-experienced T cells in murine tumors, and that these cells were more heterogeneously distributed than in untreated tumors (199). As observed in other models and discussed above, in these untreated murine tumor models T cells exhibited greater motility in the tumor periphery than in the tumor core (199). Following PDL1 blockade alone or combined PDL1 and CTLA4 blockade T cell motility was decreased in all regions of the tumor and overall infiltration was increased (199), consistent with increased cognate interactions in the tumor environment.…”

Section: Effect Of Checkpoint Regulators On Retentionmentioning

confidence: 99%

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The Dynamic Entropy of Tumor Immune Infiltrates: The Impact of Recirculation, Antigen-Specific Interactions, and Retention on T Cells in Tumors

et al. 2021

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Analysis of tumor infiltration using conventional methods reveals a snapshot view of lymphocyte interactions with the tumor environment. However, lymphocytes have the unique capacity for continued recirculation, exploring varied tissues for the presence of cognate antigens according to inflammatory triggers and chemokine gradients. We discuss the role of the inflammatory and cellular makeup of the tumor environment, as well as antigen expressed by cancer cells or cross-presented by stromal antigen presenting cells, on recirculation kinetics of T cells. We aim to discuss how current cancer therapies may manipulate lymphocyte recirculation versus retention to impact lymphocyte exclusion in the tumor.

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Section: Effect Of Checkpoint Regulators On Retentionsupporting

confidence: 74%

Section: Effect Of Checkpoint Regulators On Retentionmentioning

confidence: 88%

Section: Effect Of Checkpoint Regulators On Retentionmentioning

confidence: 99%

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The Dynamic Entropy of Tumor Immune Infiltrates: The Impact of Recirculation, Antigen-Specific Interactions, and Retention on T Cells in Tumors

et al. 2021

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“…We suggest analyzing the spatial architecture of the TIME in terms of temporal dynamics. For example, with superresolution intravital fluorescence microscopy, a prospective study can be carried out to investigate T cell behavior within specimens collected before and after immunotherapy to identify spatial structural changes ( 212 ). The description and tracking of the spatiotemporal heterogeneity and evolution of the TIME will provide additional insights into tumor diagnosis and treatment.…”

Section: Discussionmentioning

confidence: 99%

Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response

et al. 2021

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Tumors are not only aggregates of malignant cells but also well-organized complex ecosystems. The immunological components within tumors, termed the tumor immune microenvironment (TIME), have long been shown to be strongly related to tumor development, recurrence and metastasis. However, conventional studies that underestimate the potential value of the spatial architecture of the TIME are unable to completely elucidate its complexity. As innovative high-flux and high-dimensional technologies emerge, researchers can more feasibly and accurately detect and depict the spatial architecture of the TIME. These findings have improved our understanding of the complexity and role of the TIME in tumor biology. In this review, we first epitomized some representative emerging technologies in the study of the spatial architecture of the TIME and categorized the description methods used to characterize these structures. Then, we determined the functions of the spatial architecture of the TIME in tumor biology and the effects of the gradient of extracellular nonspecific chemicals (ENSCs) on the TIME. We also discussed the potential clinical value of our understanding of the spatial architectures of the TIME, as well as current limitations and future prospects in this novel field. This review will bring spatial architectures of the TIME, an emerging dimension of tumor ecosystem research, to the attention of more researchers and promote its application in tumor research and clinical practice.

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“…Magnetic nanoparticles and fluorine-19 perfluorocarbon labelling of cells offers the opportunity to track cells without the use of ionising radiation but is limited by the low sensitivity of MRI and MR spectroscopy (MRS), as well as significant concentration of contrast agents that are required for detection [10,11]. Although cell tracking using optical imaging can provide valuable insights on single cell behaviour and cell-cell interactions at a microscopic level [12], the poor tissue penetrance of light and the limited spatial resolution of these techniques at a whole-body level, has limited the clinical application of optical imaging [13].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Cell Tracking Using PET: Opportunities and Challenges for Clinical Translation in Oncology

Lechermann

Lau

Attili

et al. 2021

Cancers

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Cell therapy is a rapidly evolving field involving a wide spectrum of therapeutic cells for personalised medicine in cancer. In vivo imaging and tracking of cells can provide useful information for improving the accuracy, efficacy, and safety of cell therapies. This review focuses on radiopharmaceuticals for the non-invasive detection and tracking of therapeutic cells using positron emission tomography (PET). A range of approaches for imaging therapeutic cells is discussed: Direct ex vivo labelling of cells, in vivo indirect labelling of cells by utilising gene reporters, and detection of specific antigens expressed on the target cells using antibody-based radiopharmaceuticals (immuno-PET). This review examines the evaluation of PET imaging methods for therapeutic cell tracking in preclinical cancer models, their role in the translation into patients, first-in-human studies, as well as the translational challenges involved and how they can be overcome.

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Intravital Imaging of Adoptive T-Cell Morphology, Mobility and Trafficking Following Immune Checkpoint Inhibition in a Mouse Melanoma Model

Cited by 29 publications

References 59 publications

The Dynamic Entropy of Tumor Immune Infiltrates: The Impact of Recirculation, Antigen-Specific Interactions, and Retention on T Cells in Tumors

The Dynamic Entropy of Tumor Immune Infiltrates: The Impact of Recirculation, Antigen-Specific Interactions, and Retention on T Cells in Tumors

Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response

In Vivo Cell Tracking Using PET: Opportunities and Challenges for Clinical Translation in Oncology

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