Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma

Coy, Shannon; Rashid, Rumana; Lin, Jia-Ren; Du, Ziwei; Donson, Andrew M.; Hankinson, Todd C.; Foreman, Nicholas; Manley, Peter; Kieran, Mark W.; Reardon, David A.; Sorger, Peter K.; Santagata, Sandro

doi:10.1093/neuonc/noy035

Cited by 74 publications

(63 citation statements)

References 39 publications

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“…For some samples, we have demonstrated preservation of structure out to the limits of super-resolution optical microscopes (about 140 nm laterally) 9 . To date, we have tested primary antibodies against cell cycle regulators, signaling proteins and kinases, cell lineage markers, transcription factors, a wide array of cell state markers 9 , and multiple immune markers (see https://www.cycif.org/ for details) 9,40,41 . Efforts are also underway to integrate multiplex immunofluorescence imaging with FISH, in situ mRNA profiling and DNA mutation detection 42,43,43,44 as part of a multi-parametric approach to tumor characterization and human tumor atlas construction.…”

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confidence: 99%

Qualifying antibodies for image-based immune profiling and multiplexed tissue imaging

et al. 2019

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Spatially resolved, multiplexed tissue imaging makes it possible to characterize cell types and states in human resection specimens, xenografts and animal tissues. A growing number of tissue imaging methods applicable to standard formaldehyde fixed paraffin embedded (FFPE) tissue sections have been described, the vast majority of which rely on antibodies for antigen detection and mapping. This protocol focuses on methods for confirming the selectivity and specificity of such antibodies for constructing and validating antibody panels. Although we use tissue-based cyclic immunofluorescence (t-CyCIF) as an imaging approach, the antibody testing methods we described are broadly applicable. We demonstrate the protocol by assembling a 16-antibody panel designed to enumerate and localize T-cells and B-cells, macrophages, and cells expressing immune checkpoint regulators in tumor resection specimens and by showing how the panel performs in the identification of common and rare immune cell types in lung cancer.

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confidence: 99%

Qualifying antibodies for image-based immune profiling and multiplexed tissue imaging

et al. 2019

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“…8,67 Recent support for the roles of PD-1 and PD-L1 in ACP provides another new avenue for potential systemic treatment. 16 Coy and colleagues described consistent and unique localization patterns of upregulated expression of intrinsic PD-1 and PD-L1 in ACP. 16 Elevated expressions of PD-1 were found only in nuclear β-catenin-accumulating cell clusters.…”

Section: The Programmed Cell Death Pathwaymentioning

confidence: 91%

“…16 Coy and colleagues described consistent and unique localization patterns of upregulated expression of intrinsic PD-1 and PD-L1 in ACP. 16 Elevated expressions of PD-1 were found only in nuclear β-catenin-accumulating cell clusters. 16 In melanoma, PD-1 expression has been linked to tumorigenesis through the downstream activation of MAPK/ERK.…”

Section: The Programmed Cell Death Pathwaymentioning

confidence: 91%

Adamantinomatous craniopharyngioma: moving toward targeted therapies

Hengartner

Prince

Vijmasi

et al. 2020

Neurosurgical Focus

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The evolving characterization of the biological basis of adamantinomatous craniopharyngioma (ACP) has provided insights critical for novel systemically delivered therapies. While current treatment strategies for ACP are associated with low mortality rates, patients experience severely lowered quality of life due to high recurrence rates and chronic sequelae, presenting a need for novel effective treatment regimens. The identification of various dysregulated pathways that play roles in the pathogenesis of ACP has prompted the investigation of novel treatment options. Aberrations in the CTNNB1 gene lead to the dysregulation of the Wnt pathway and the accumulation of nuclear β-catenin, which may play a role in tumor invasiveness. While Wnt pathway/β-catenin inhibition may be a promising treatment for ACP, potential off-target effects have limited its use in current intervention strategies. Promising evidence of the therapeutic potential of cystic proinflammatory mediators and immunosuppressants has been translated into clinical therapies, including interleukin 6 and IDO-1 inhibition. The dysregulation of the pathways of mitogen-activated protein kinase/extracellular signal–regulated kinase (MAPK/ERK), epidermal growth factor receptor (EGFR), and programmed cell death protein 1 and its ligand (PD-1/PD-L1) has led to identification of various therapeutic targets that have shown promise as clinical strategies. The Sonic Hedgehog (SHH) pathway is upregulated in ACP and has been implicated in tumorigenesis and tumor growth; however, inhibition of SHH in murine models decreased survival, limiting its therapeutic application. While further preclinical and clinical data are needed, systemically delivered therapies could delay or replace the need for more aggressive definitive treatments. Ongoing preclinical investigations and clinical trials of these prospective pathways promise to advance treatment approaches aimed to increase patients’ quality of life.

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“…A common application of tissue imaging in oncology, for example, is identifying and enumerating immune cell types and mapping their locations relative to tumor and stromal cells 5 . Such spatially-resolved data is pertinent to understanding the mechanisms of action of immunotherapies (e.g., immune checkpoint inhibitors) 6 that function by blocking juxtracrine signaling between immune and tumor cells. Whole slide tissue images are complex however: when data are acquired using a fluorescence microscope, structures ranging in size by over five orders of magnitude are visible, from subcellular vesicles and nuclear granules to configurations of multiple cells such as blood vessels.…”

Section: Main Textmentioning

confidence: 99%

Online narrative guides for illuminating tissue atlas data and digital pathology images

Rashid

Yuan

Hoffer

et al. 2020

Preprint

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The recent introduction of highly multiplexed imaging of human tissues and tumors promises to fundamentally advance research in tissue biology and human disease. At the same time, histopathology in the clinical setting is undergoing a rapid transition to digital methods. Thus, repositories of imaging data from research and clinical specimens will soon join genomic databases as a means to systematically explore the molecular basis of disease. Even with recent advances in machine learning, experience in anatomic pathology has shown that there is no substitute for expert visual review, annotation, and description of image data. We review the ecosystem of software available for atlas and histopathology images and introduce a new Web-based software tool, Minerva Story, that addresses a critical unmet need. Minerva is an interpretative and interactive guide to complex images organized around guided analysis. We discuss how Minerva and similar software will be integrated into multi-omic browsers for data dissemination of future atlases.

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Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma

Cited by 74 publications

References 39 publications

Qualifying antibodies for image-based immune profiling and multiplexed tissue imaging

Qualifying antibodies for image-based immune profiling and multiplexed tissue imaging

Adamantinomatous craniopharyngioma: moving toward targeted therapies

Online narrative guides for illuminating tissue atlas data and digital pathology images

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