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Cancers
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Multiplexed Imaging for Cancer Diagnosis and Therapy: Dissecting Networks at...
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Multiplexed Imaging for Cancer Diagnosis and Therapy: Dissecting Networks at Tissue or Single-Cell Level

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: closed (28 April 2023) | Viewed by 16549

Special Issue Editor

Dr. Roberto Benelli

E-Mail Website
Guest Editor
SSD Molecular Oncology and e Angiogenesis, IRCCS Ospedale Policlinico San Martino, Viale Rosanna Benzi 10, 16132 Genoa, Italy
Interests: colorectal cancer; tumor microenvironment; immunohistochemistry; intracellular signaling; 3D primary cultures; organoids; EGFR; Akt; Erk; COX2
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The need to co-localize several markers at tissue or cellular level has a long history. Starting from the early use of serial tissue sections in white field microscopy to double/triple immunofluorescence/confocal microscopy of cultured cell lines, these techniques have recently evolved into high throughput platforms integrating new detection techniques, imaging software, and artificial intelligence analysis. Multiplexed imaging can now surpass the efficiency of cytofluorimetric analysis, as a similar information output (single-cell antigen coexpression quantification) is now linked to the spatial distribution of the analyzed markers in tissue/cell compartments. These techniques allow the precise identification of any single cell within a tissue and to dissect the complex communication network in which it is involved. The recent literature shows a boost in these techniques, which are frequently applied to cancer for microenvironmental or immunological studies.

This thematic issue would like to showcase the numerous multiplexed imaging techniques (from those affordable enough for any lab with standard equipment to more innovative examples) and to demonstrate their impact on cancer diagnosis and therapy. Studies on specific software and AI algorithms are also welcome, so long as they are applied to cancer.

Dr. Roberto Benelli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • imaging
  • multiplex
  • spectral imaging
  • imaging mass cytometry
  • interactome
  • white field microscopy
  • confocal microscopy
  • immunohistochemistry
  • bar coded probe
  • imaging software
  • artificial intelligence

Published Papers (4 papers)

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Research

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16 pages, 1353 KiB  
Article
Comparing and Correcting Spectral Sensitivities between Multispectral Microscopes: A Prerequisite to Clinical Implementation
by Margaret Eminizer, Melinda Nagy, Elizabeth L. Engle, Sigfredo Soto-Diaz, Andrew Jorquera, Jeffrey S. Roskes, Benjamin F. Green, Richard Wilton, Janis M. Taube and Alexander S. Szalay
Cancers 2023, 15(12), 3109; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15123109 - 08 Jun 2023
Viewed by 1130
Abstract
Multispectral, multiplex immunofluorescence (mIF) microscopy has been used to great effect in research to identify cellular co-expression profiles and spatial relationships within tissue, providing a myriad of diagnostic advantages. As these technologies mature, it is essential that image data from mIF microscopes is [...] Read more.
Multispectral, multiplex immunofluorescence (mIF) microscopy has been used to great effect in research to identify cellular co-expression profiles and spatial relationships within tissue, providing a myriad of diagnostic advantages. As these technologies mature, it is essential that image data from mIF microscopes is reproducible and standardizable across devices. We sought to characterize and correct differences in illumination intensity and spectral sensitivity between three multispectral microscopes. We scanned eight melanoma tissue samples twice on each microscope and calculated their average tissue region flux intensities. We found a baseline average standard deviation of 29.9% across all microscopes, scans, and samples, which was reduced to 13.9% after applying sample-specific corrections accounting for differences in the tissue shown on each slide. We used a basic calibration model to correct sample- and microscope-specific effects on overall brightness and relative brightness as a function of the image layer. We tested the generalizability of the calibration procedure and found that applying corrections to independent validation subsets of the samples reduced the variation to 2.9 ± 0.03%. Variations in the unmixed marker expressions were reduced from 15.8% to 4.4% by correcting the raw images to a single reference microscope. Our findings show that mIF microscopes can be standardized for use in clinical pathology laboratories using a relatively simple correction model. Full article
(This article belongs to the Special Issue Multiplexed Imaging for Cancer Diagnosis and Therapy: Dissecting Networks at Tissue or Single-Cell Level)
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Review

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30 pages, 6040 KiB  
Review
Multiplex Tissue Imaging: Spatial Revelations in the Tumor Microenvironment
by Stephanie van Dam, Matthijs J. D. Baars and Yvonne Vercoulen
Cancers 2022, 14(13), 3170; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14133170 - 28 Jun 2022
Cited by 15 | Viewed by 7528
Abstract
The tumor microenvironment is a complex ecosystem containing various cell types, such as immune cells, fibroblasts, and endothelial cells, which interact with the tumor cells. In recent decades, the cancer research field has gained insight into the cellular subtypes that are involved in [...] Read more.
The tumor microenvironment is a complex ecosystem containing various cell types, such as immune cells, fibroblasts, and endothelial cells, which interact with the tumor cells. In recent decades, the cancer research field has gained insight into the cellular subtypes that are involved in tumor microenvironment heterogeneity. Moreover, it has become evident that cellular interactions in the tumor microenvironment can either promote or inhibit tumor development, progression, and drug resistance, depending on the context. Multiplex spatial analysis methods have recently been developed; these have offered insight into how cellular crosstalk dynamics and heterogeneity affect cancer prognoses and responses to treatment. Multiplex (imaging) technologies and computational analysis methods allow for the spatial visualization and quantification of cell–cell interactions and properties. These technological advances allow for the discovery of cellular interactions within the tumor microenvironment and provide detailed single-cell information on properties that define cellular behavior. Such analyses give insights into the prognosis and mechanisms of therapy resistance, which is still an urgent problem in the treatment of multiple types of cancer. Here, we provide an overview of multiplex imaging technologies and concepts of downstream analysis methods to investigate cell–cell interactions, how these studies have advanced cancer research, and their potential clinical implications. Full article
(This article belongs to the Special Issue Multiplexed Imaging for Cancer Diagnosis and Therapy: Dissecting Networks at Tissue or Single-Cell Level)
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25 pages, 1591 KiB  
Review
Dissecting Tumor-Immune Microenvironment in Breast Cancer at a Spatial and Multiplex Resolution
by Evangelos Tzoras, Ioannis Zerdes, Nikos Tsiknakis, Georgios C. Manikis, Artur Mezheyeuski, Jonas Bergh, Alexios Matikas and Theodoros Foukakis
Cancers 2022, 14(8), 1999; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14081999 - 14 Apr 2022
Cited by 6 | Viewed by 4820
Abstract
The tumor immune microenvironment (TIME) is an important player in breast cancer pathophysiology. Surrogates for antitumor immune response have been explored as predictive biomarkers to immunotherapy, though with several limitations. Immunohistochemistry for programmed death ligand 1 suffers from analytical problems, immune signatures are [...] Read more.
The tumor immune microenvironment (TIME) is an important player in breast cancer pathophysiology. Surrogates for antitumor immune response have been explored as predictive biomarkers to immunotherapy, though with several limitations. Immunohistochemistry for programmed death ligand 1 suffers from analytical problems, immune signatures are devoid of spatial information and histopathological evaluation of tumor infiltrating lymphocytes exhibits interobserver variability. Towards improved understanding of the complex interactions in TIME, several emerging multiplex in situ methods are being developed and gaining much attention for protein detection. They enable the simultaneous evaluation of multiple targets in situ, detection of cell densities/subpopulations as well as estimations of functional states of immune infiltrate. Furthermore, they can characterize spatial organization of TIME—by cell-to-cell interaction analyses and the evaluation of distribution within different regions of interest and tissue compartments—while digital imaging and image analysis software allow for reproducibility of the various assays. In this review, we aim to provide an overview of the different multiplex in situ methods used in cancer research with special focus on breast cancer TIME at the neoadjuvant, adjuvant and metastatic setting. Spatial heterogeneity of TIME and importance of longitudinal evaluation of TIME changes under the pressure of therapy and metastatic progression are also addressed. Full article
(This article belongs to the Special Issue Multiplexed Imaging for Cancer Diagnosis and Therapy: Dissecting Networks at Tissue or Single-Cell Level)
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Other

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11 pages, 1272 KiB  
Systematic Review
Non-Melanoma Skin Cancer Clearance after Medical Treatment Detected with Noninvasive Skin Imaging: A Systematic Review and Meta-Analysis
by Stefania Guida, Antonio Alma, Kaleci Shaniko, Johanna Chester, Silvana Ciardo, Ilaria Proietti, Roberta Giuffrida, Iris Zalaudek, Marco Manfredini, Caterina Longo, Francesca Farnetani and Giovanni Pellacani
Cancers 2022, 14(12), 2836; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14122836 - 08 Jun 2022
Cited by 6 | Viewed by 2038
Abstract
Background/Objectives: Non-melanoma skin cancer (NMSC) treated with nonsurgical therapies can be monitored with noninvasive skin imaging. The precision of dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in detecting clearance is unclear. We aim to report the proportion of persisting tumors [...] Read more.
Background/Objectives: Non-melanoma skin cancer (NMSC) treated with nonsurgical therapies can be monitored with noninvasive skin imaging. The precision of dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in detecting clearance is unclear. We aim to report the proportion of persisting tumors identified with noninvasive technologies available in the literature. Methods: A systematic literature search was conducted on the PubMed and Cochrane Public Library Databases for articles published prior to November 2021. Statistical analyses were conducted with MedCalc 14.8.1 software. Results: A total of eight studies (352 lesions) reporting noninvasive imaging for NMSC clearance following nonsurgical treatment were included. Most (n = 7) reported basal cell carcinoma (BCC), and one study reported squamous cell carcinoma (SCC) clearance. A meta-analysis of the BCC clearance revealed that the summary effect for RCM was higher, as compared to the other techniques. Interestingly, the sensitivity and specificity for OCT were 86.4% (95% CI: 65.1–97.1) and 100% (95% CI: 94.8–100.0), respectively, whilst, for RCM, they reached 100% (95%CI: 86.8–100) and 72.5% (95% CI: 64.4–79.7), respectively. Conclusions: Routine clinical examination and dermoscopy underperform when employed for NMSC clearance monitoring, although they represent the first approach to the patient. OCT and RCM seem to improve the detection of persistent BCC after medical treatment. Full article
(This article belongs to the Special Issue Multiplexed Imaging for Cancer Diagnosis and Therapy: Dissecting Networks at Tissue or Single-Cell Level)
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