Danielle Guerrero

Mechanical regulation of glycolysis via cytoskeleton architecture

HALO Publications, Publications / , , ,

Jin Suk Park,et al, Nature, 2020.
Park and colleagues explored the question of how regulation of glycolysis responds to structural changes in tissue architecture and chose lung cells and tissue for their studies due to the regular mechanical stress experienced during respiration. In vitro studies demonstrated downregulation of glycolysis following a change in substrate via the degradation of the platelet isoform of the phosphofructokinase (PFKP) enzyme. In vitro studies also showed that oncogenic transformation changed the ability of PFKP expression to change in response to mechanical stress. The researchers corroborated this result with in vivo work by performing immunohistochemical assays on control and malignant tissue cores from bronchi of lung cancer patients. The HALO Tissue Classifier Add-on was used to classify epithelium, stroma, and tumor within the tissue cores and the Cytonuclear IHC module was used to quantify cytoplasmic PFKP staining in bronchial epithelium.

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Association of COVID-19 inflammation with activation of the C5a–C5aR1 axis

Publications /

Julien Carvelli, et al, Nature, 2020
Researchers aiming to block excessive lung inflammation in COVID-19 patients found upregulated immune checkpoint biomarkers in patients with a range of COVID-19 symptoms (from paucisymptomatic to acute respiratory distress syndrome). In addition, Carvelli et al found increased expression of C5a, an inflammatory mediator, in serum and the C5aR1 receptor on myeloid cells in COVID-19 patients, which are known to initiate inflammatory responses by recruiting neutrophils and monocytes to lungs. An in vitro neutrophil migration assay quantified with the CytoNuclear FL Module of HALO demonstrated that the clinical stage therapeutic monoclonal antibody, avdoralimab, effectively inhibited C5a-induced neutrophil migration. The authors propose use of avdoralimab to limit excessive lung inflammation associated with acute respiratory distress in COVID-19 patients.

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Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions

HALO Publications, Publications /

Jules Russick, et al, Journal for ImmunoTherapy of Cancer, 2020.
Natural killer (NK) cells are known to have cytotoxic effector functions in tumor immunosurveillance. More recently, evidence of a second potentially inhibitory or regulatory role have emerged. Here, Russick et al compared expression patterns of NK cells inside tumors to nontumoral NK cells to understand their inhibitory functions in the context of the non-small cell lung carcinoma (NSCLC) tumor microenvironment (TME). These studies identified a novel and specific gene signature of NK cells dysregulation in NSCLC that suggests that the TME may induce suppressive NK cells. HALO image analysis software was leveraged to quantify CD8 expression of formalin fixed paraffin embedded NSCLC sections with CD8 immunohistochemistry and a hematoxylin counterstain. While the presence of CD8 was previously known to be associated with good clinical outcomes, Russick and colleagues uncovered a more complex relationship where patients with low CD8+ T cells and high NK cell density had good outcomes, and those with high CD8+ T cells and high NK cell density had poor outcomes.

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Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival

HALO Publications, Publications / , ,

Sandeep K Singhal, et al, Communications Biology, 2021.
Singhal and colleagues apply quantitative automated image analysis to investigate the role of a transcriptional regulator, Kaiso, in a diverse cohort of breast cancer tumors. Specifically, they utilized the Highplex FL Module with the Tissue Microarray Module of HALO to characterize the tumor microenvironment in breast cancer TMA cores, including pan-cytokeratin, PD-L1, CD8, and CD68. They found that cytoplasmic Kaiso is associated with an immune-suppressed tumor microenvironment and found novel connections between Kaiso and autophagy-related proteins LC3A/B that are associated with breast cancer subtype and survival. The mechanism(s) by which Kaiso promotes tumor progression will require future investigation.

Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival Read More »

Intratumoral interleukin-12 mRNA therapy promotes TH1 transformation of the tumor microenvironment

HALO Publications, Immuno-Oncology, Publications / ,

Susannah L Hewitt, et al, Clinical Cancer Research, 2020.
In patients with advanced stage lung disease, it is beneficial to evaluate candidacy for immunotherapy without invasive biopsy testing. Lou et al performed a concordance study to evaluate formalin fixed cell blocks compared to lung tumor resections using a PD-L1 22C3 IHC pharmDx™ assay and found strong concordance between pathologists and HALO image analysis software. Future research will focus on clinical validation by assessing the clinical benefit from immunotherapy following PD-L1 immunohistochemistry on cytology specimens.

Intratumoral interleukin-12 mRNA therapy promotes TH1 transformation of the tumor microenvironment Read More »

Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein

HALO Publications, Publications /

Chris McKinnon, et al, Acta Neuropathologica Communications, 2020.
In this study, McKinnon et al identify overexpression of α-synuclein leading to catalytic impairment of the 26S proteosome in defined regions of rat brains. Brain tissue was fixed following α-synuclein overexpression for immunofluorescence studies of dopaminergic neurons which were quantified by the HALO image analysis platform. Future research will focus on characterizing the relationship between proteasome impairment and neurodegeneration.

Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein Read More »

Implementation of PD-L1 22C3 IHC pharmDxTM in Cell Block Preparations of Lung Cancer: Concordance with Surgical Resections and Technical Validation of CytoLyt® Prefixation

HALO Publications, Oncology, Publications / ,

Si Kei Lou, et al, Acta Cytologica, 2020.
In patients with advanced stage lung disease, it is beneficial to evaluate candidacy for immunotherapy without invasive biopsy testing. Lou et al performed a concordance study to evaluate formalin fixed cell blocks compared to lung tumor resections using a PD-L1 22C3 IHC pharmDx™ assay and found strong concordance between pathologists and HALO image analysis software. Future research will focus on clinical validation by assessing the clinical benefit from immunotherapy following PD-L1 immunohistochemistry on cytology specimens.

Implementation of PD-L1 22C3 IHC pharmDxTM in Cell Block Preparations of Lung Cancer: Concordance with Surgical Resections and Technical Validation of CytoLyt® Prefixation Read More »

Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration

HALO AI Publications, Publications

Alan M. Race, et al, Analytical Chemistry, 2021
With increasing demand to correlate data across multiple imaging modalities, Race and colleagues demonstrate a mechanism by which annotations can be generated on images from one imaging modality and transferred to a second image modality for data integration (and optionally, back again). Further, they perform this workflow on mass spectrometry images of a pancreatic cancer mouse model and hematoxylin and eosin-stained sections. HALO and HALO AI image analysis software was used to develop a DenseNet algorithm to classify and generate annotations for pancreatic ductal carcinoma tumor, non-neoplastic acinar tissue, and connective tissue on H&E-stained slides. This method for bidirectional transfer of image annotations may enable novel workflows in the future.

Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration Read More »

Maternal obesity during pregnancy leads to adipose tissue ER stress in mice via miR-126-mediated reduction in Lunapark

HALO AI Publications, Publications

Juliana de Almeida-Faira, et al, Diabetologia, 2021
In this study, researchers set out to understand how miR-126-3, a microRNA found at increased levels in offspring of maternally obese mice, functioned in adipocyte metabolism. de Almeida-Faria and colleagues used proteomic approaches to identify a novel ER protein that is a direct target of miR-126-3 called Lunapark. HALO and HALO AI were used to train a DenseNet algorithm to selectively identify crown-like structures in H&E-stained fat tissue. Further, de Almeida-Faria and colleagues demonstrate that maternal obesity in mice leads to an increased risk of type 2 diabetes in offspring by targeting miR-126-3 regulation. Therefore, miR-126-3 is identified as a potential therapeutic target that could impact obesity and type 2 diabetes.

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Tumoral PD-1hiCD8+ T cells are partially exhausted and predict favorable outcome in triple-negative breast cancer

HALO AI Publications, Publications

Liang Guo, et al, Clinical Science, 2020
Prior to this publication it was known that dysfunctional PD-1hi CD8+ T cells infiltrated tumors, although it was unknown if this phenotype played a role in triple-negative breast cancer (TNBC). Guo et al set out to explore this phenotype in triple-negative breast cancer and using HALO and HALO AI demonstrated using both quantitative multiplexed immunohistochemistry and multispectral fluorescence imaging that PD-1hi CD8+ T cells were found in TNBC patient tissue biopsy core analysis but largely absent from peripheral blood. Molecular analysis of these cells revealed expression of biomarkers associated with T-cell exhaustion and the authors hypothesize that this cellular phenotype could be useful for future stratification and as a prognostic marker in TNBC patients as the presence of PD-1hi CD8+ T cells are associated with favorable outcomes. In addition, future research with this cellular phenotype may provide opportunity for therapeutic advancement in TNBC, a challenging subtype of breast cancer to treat.

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