Danielle Guerrero

An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer

HALO Publications, Publications /

Paula Voabil,et al, Nature Medicine, 2021.
Dr. Paula Voabil and colleagues used a patient derived tumor fragment platform to investigate immune responses immediately following PD-1 blockade. The Tissue Classifier Add-on and the Multiplex IHC module of HALO® were used in this publication to quantify immune biomarkers in the tumor and stroma, contributing to their conclusion that the ability of tumors to respond to PD-1 blockage correlates with the ability of intratumoral immune cells to be reactivated by the blockade.

An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer Read More »

Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers

HALO Publications, Immuno-Oncology, Publications /

Myriam Chalabi, et al, Nature Medicine, 2020.
Immunotherapy is known to be effective in late-stage, mismatch repair (MMR) deficient colorectal cancers but not in MMR proficient cancer. This study reports the early results from the NICHE clinical trial that is evaluating treatment of early stage, nonmetastatic preoperative colon cancer with a CTLA-4 inhibitor and a PD-1 inhibitor. Chalabi and colleagues report that the treatment was well tolerated and that a major pathological response was seen in 19/20 patients with MMR deficient tumors and 3/15 MMR proficient tumors. HALO image analysis software was used in this publication for analysis of T-cell biomarkers CD3, CD8, and FOXP3 on chromogenically stained tumor biopsies. First, image registration with HALO was performed of three serial tissue sections. Tissue sections were annotated manually, and quantification of DAB positivity was performed with the Multiplex IHC module and expressed as a function of tumor area. The authors conclude that immunotherapy shows promise to become the standard of care in a defined group of early-stage colon cancers.

Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers Read More »

Transmission of tauopathy strains is independent of their isoform composition

HALO Publications, Publications

Alexander Jaisl, et al, Neuron, 2020.
To advance the molecular understanding of obesity, Jais and colleagues set out to identify neuronal populations in mice that respond to being fed a calorie dense, highly palatable food. They identified prepronociceptin (PNOC)-expressing neurons in the hypothalamus that are activated upon acute high fat diet feeding and promote overconsumption. In this publication, HALO image analysis software was used for quantification of transgene expression in mouse neuronal tissue. Future studies on PNOC-expressing neurons may advance prevention and treatment of obesity and associated metabolic diseases.

Transmission of tauopathy strains is independent of their isoform composition Read More »

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.

Mechanical regulation of glycolysis via cytoskeleton architecture Read More »

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.

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

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.

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

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 »

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