HALO Publications

SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence

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SARS-CoV-2, the causative agent of COVID-19, has been the focus of intense research since its detection in late 2019. It is known that viral infection affects several cellular processes, including senescence and inflammation, and prior studies also point toward SARS-CoV-2 infection causing engagement of components of the DNA damage repair machinery. However, questions remain about …

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Cellular mechanisms of heterogeneity in NF2-mutant schwannoma

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Schwannomas are sporadic, usually benign tumors that develop predominately on spinal nerve roots and cranial nerves. Inactivation of NF2 in Schwann cells (SC) is the cause of nearly all schwannomas and mutations in additional genes are few if present at all. Despite their genetic similarity, NF2-mutant schwannomas are characterized by significant variability, exhibiting diverse natural …

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Modulation of the Human Pancreatic Ductal Adenocarcinoma Immune Microenvironment by Stereotactic Body Radiotherapy

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Stereotactic body radiotherapy (SBRT) uses multiple targeted beams of radiation to damage malignant cells while limiting effects to surrounding tissue. SBRT is a standard treatment for various cancers that elicit strong immune responses, but immunologically cold tumors, such as pancreatic ductal adenocarcinoma (PDAC), are often refractory. SBRT has been shown to promote opposing antitumor and …

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Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma

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Jason Yongsheng Chan,et al, The Journal of Clinical Investigation, 2020.
To molecularly characterize the rare and aggressive tumors known as angiosarcomas, Chan et al utilized a combination of transcriptomic immuno-oncology profiling with multiplex immunohistochemistry and immunofluorescence. HALO image analysis software was used for the quantification of PD-L1, CD68, CD8, FOXP3, CD15, and ERG. From these studies, three phenotypes of patients were identified according to etiology, anatomical origin, signaling pathways, and the tumor inflammation signature. These distinct biological phenotypes provide opportunity for future studies to improve prognosis and treatment of a rare and deadly disease.

PNOCARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding

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.

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

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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.

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.

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.

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.

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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