HALO Publications

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 »

Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

Area Quantification, COVID-19, HALO Publications, Infectious Disease, Multiplex IHC, Publications

Lisa H Tostanoski, et al, Nature Medicine, 2020.
In this study led by researchers at Harvard Medical School, they report the first demonstration of prevention of severe clinical disease in a hamster model of SARS-CoV-2 that were provided with a single immunization of the adenovirus serotype 26 (Ad26) vaccine. The Ad26 vaccine utilizes a stabilized spike protein of the SARS-CoV-2 and in the United States this vaccine is commonly known as the Johnson and Johnson vaccine. This study, published in print in November 2020 contributed to the scientific body of evidence in animal models that enabled clinical vaccine trials that in turn led to emergency use approvals in the United States, Canada, and other countries. Researchers leveraged the Multiplex IHC module of HALO for evaluation of the percentage of SAR-N protein positive cells and for Iba-1 quantification. The Area Quantification IHC module was used to determine the percentage of SARS-CoV-2 sense or anti-sense probe or Mx1 protein as a function of area. The Cytonuclear IHC module and Area Quantification IHC modules were used in detection of MPO+ or CD3+ cells expressed as a proportion of total alveolar tissue.

Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters Read More »

Digital image analysis improves precision of PD‐L1 scoring in cutaneous melanoma

HALO Publications, Multiplex IHC, Publications /

Viktor H. Koelzer, et al, Nature Medicine, 2018. Immune checkpoint inhibitors have become a successful treatment in metastatic melanoma. The high response rates in a subset of patients suggest that a sensitive companion diagnostic test is required. The predictive value of programmed death ligand 1 (PD‐L1) staining in melanoma has been questioned due to inconsistent correlation with clinical outcome. Whether this is due to predictive irrelevance of PD‐L1 expression or inaccurate assessment techniques remains unclear. The aim of this study was to develop a standardised digital protocol for the assessment of PD‐L1 staining in melanoma and to compare the output data and reproducibility to conventional assessment by expert pathologists.

Digital image analysis improves precision of PD‐L1 scoring in cutaneous melanoma Read More »

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