HALO Modules

Monomeric/dimeric forms of Fgf15/FGF19 show differential activity in hepatocyte proliferation and metabolic function

Courtney M. Williams et al, The FASEB Journal, 2021
Williams and colleagues at Regeneron Pharmaceuticals perform structure/function relationship studies on Fgf15 and FGF19 using site-directed mutagenesis and downstream functional assays in order to understand their distinct functions in a common pathway. Both molecules are therapeutic targets due to involvement in hepatocellular carcinoma and bile acid production. This publication identifies a single cysteine residue is identified that controls dimerization and hepatocyte proliferation. Understanding these molecular pathways may inform future studies on hepatocellular carcinoma while limiting toxicity and induction of hepatocyte proliferation. Immunohistochemistry images were quantified in HALO Link using the Cytonuclear IHC module.

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

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.

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

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.

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