Overview of multiplex immunohistochemistry/immunofluorescence techniques in the era of cancer immunotherapy

Cancer Communications, Journal Year: 2020, Volume and Issue: 40(4), P. 135 - 153

Published: April 1, 2020

Abstract Conventional immunohistochemistry (IHC) is a widely used diagnostic technique in tissue pathology. However, this associated with number of limitations, including high inter‐observer variability and the capacity to label only one marker per section. This review details various highly multiplexed techniques that have emerged circumvent these constraints, allowing simultaneous detection multiple markers on single section comprehensive study cell composition, cellular functional cell‐cell interactions. Among techniques, multiplex Immunohistochemistry/Immunofluorescence (mIHC/IF) has be particularly promising. mIHC/IF provides high‐throughput staining standardized quantitative analysis for reproducible, efficient cost‐effective studies. immediate potential translational research clinical practice, era cancer immunotherapy.

Language: Английский

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CytoMAP: A Spatial Analysis Toolbox Reveals Features of Myeloid Cell Organization in Lymphoid Tissues

Cell Reports, Journal Year: 2020, Volume and Issue: 31(3), P. 107523 - 107523

Published: April 1, 2020

Recently developed approaches for highly multiplexed imaging have revealed complex patterns of cellular positioning and cell-cell interactions with important roles in both cellular- tissue-level physiology. However, tools to quantitatively study patterning tissue architecture are currently lacking. Here, we develop a spatial analysis toolbox, the histo-cytometric multidimensional pipeline (CytoMAP), which incorporates data clustering, positional correlation, dimensionality reduction, 2D/3D region reconstruction identify localized networks reveal features organization. We apply CytoMAP microanatomy innate immune subsets murine lymph nodes (LNs) mutually exclusive segregation migratory dendritic cells (DCs), regionalized compartmentalization SIRPα

Language: Английский

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IL-33-induced metabolic reprogramming controls the differentiation of alternatively activated macrophages and the resolution of inflammation

Immunity, Journal Year: 2021, Volume and Issue: 54(11), P. 2531 - 2546.e5

Published: Oct. 13, 2021

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Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 25, 2022

Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises possibility that standard care treatments delivered in concert may compromise tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models which map tumor-draining lymphatics develop for regional lymphablation with surgery or radiation. We find eliminates ICI response, worsening overall survival repolarizing tumor- peripheral-immune compartments. Mechanistically, within lymphatics, observe an upregulation conventional type I dendritic cells interferon signaling show both are necessary response lost lymphablation. Ultimately, provide a mechanistic understanding how oncologic therapies targeting impact to immune-oncology therapy order define rational, lymphatic-preserving treatment sequences mobilize systemic antitumor immunity, achieve optimal responses, control metastatic disease, confer durable immunity.

Language: Английский

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ATP and Adenosine Metabolism in Cancer: Exploitation for Therapeutic Gain

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 74(3), P. 799 - 824

Published: June 23, 2022

Adenosine is an evolutionary ancient metabolic regulator linking energy state to physiologic processes, including immunomodulation and cell proliferation. Tumors create adenosine-rich immunosuppressive microenvironment through the increased release of ATP from dying stressed cells its ectoenzymatic conversion into adenosine. Therefore, adenosine pathway becomes important therapeutic target improve effectiveness immune therapies. Prior research has focused largely on two major ectonucleotidases, ectonucleoside triphosphate diphosphohydrolase 1/cluster differentiation (CD)39 ecto-5′-nucleotidase/CD73, which catalyze breakdown extracellular adenosine, subsequent activation different subtypes receptors with mixed findings antitumor protumor effects. New findings, needed for more effective approaches, require consideration redundant pathways controlling intratumoral levels, alternative NAD-inactivating CD38-ectonucleotide pyrophosphatase phosphodiesterase (ENPP)1-CD73 axis, counteracting ATP-regenerating pathway, cellular uptake phosphorylation by kinase. This review provides a holistic view intracellular metabolism as integrated complex network summarizes recent data underlying mechanisms precursors ADP control cancer immunosurveillance, tumor angiogenesis, lymphangiogenesis, cancer-associated thrombosis, blood flow, perfusion. Special attention given differences commonalities in purinome cancers, heterogeneity microenvironment, subcellular compartmentalization system, novel roles purine-converting enzymes targets therapy.

Significance Statement

The discovery role checkpoint led development strategies targeting signaling multiple clinical trials preclinical models. Here we identify gaps knowledge that need be filled gain agents key components and, this basis, provide network.

Language: Английский

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Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(8), P. 1415 - 1433.e12

Published: July 18, 2024

Language: Английский

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Matrix-producing neutrophils populate and shield the skin

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Language: Английский

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The IBEX Imaging Knowledge-Base: A Community Resource Enabling Adoption and Development of Immunofluoresence Imaging Methods

Published: April 2, 2025

The iterative bleaching extends multiplexity (IBEX) Knowledge-Base is a central portal for researchers adopting IBEX and related 2D 3D immunofluorescence imaging methods. design of the modeled after efforts in open-source software community includes three facets: development platform (GitHub), static website, service data archiving. facilitates practice open science throughout research life cycle by providing validation recommended non-recommended reagents, e.g., primary secondary antibodies. In addition to reporting negative data, empowers method adoption evolution venue sharing protocols, videos, datasets, software, publications. A dedicated discussion forum fosters sense among while addressing questions not covered published manuscripts. Together, scientists from around world are advancing scientific discovery at faster pace, reducing wasted time effort, instilling greater confidence resulting data.

Language: Английский

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Protocol for 3D multiplexed fluorescent imaging of pulmonary TB lesions using Opal-TSA dyes for signal amplification

STAR Protocols, Journal Year: 2025, Volume and Issue: 6(1), P. 103640 - 103640

Published: Feb. 20, 2025

Language: Английский

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Topical Steroid Withdrawal Is a Targetable Excess of Mitochondrial NAD+

Journal of Investigative Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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