Multiplex IHC

Prognostic Value of CD8+ Lymphocytes in Hepatocellular Carcinoma and Perineoplastic Parenchyma Assessed by Interface Density Profiles in Liver Resection Samples

This study examined CD8+ cell distribution in hepatocellular carcinoma (HCC) and peritumoral liver tissue to investigate the overall survival (OS) and recurrence-free survival (RFS). It is well understood that CD8+ lymphocytes are involved in both the anti-tumor response and in managing hepatocyte damage in the parenchyma. Further, it was previously known that HCC often develops …

Prognostic Value of CD8+ Lymphocytes in Hepatocellular Carcinoma and Perineoplastic Parenchyma Assessed by Interface Density Profiles in Liver Resection Samples Read More »

Multiplex IHC

Quantify expression of up to five brightfield stains in any cellular compartment – membrane, nucleus or cytoplasm.

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.

Independent Prognostic Value of Intratumoral Heterogeneity and Immune Response Features by Automated Digital Immunohistochemistry Analysis in Early Hormone Receptor-Positive Breast Carcinoma

Dovile Zilenaite, et al, Frontiers in Oncology, 2020
This study by Zilenaite and colleagues evaluated the prognostic value of digital image analysis using HALO on analysis of hormone receptor positive breast cancer IHC biomarkers including ER, PR, HER2, and Ki67 combined with information on tumor heterogeneity and immune response. HALO AI was used for tissue classification to differentiate tumor, stroma, and background (necrosis, artifacts, glass). For quantitative analysis of breast cancer biomarker expression and localization, the Multiplex IHC module of HALO was used. The authors demonstrate that prognostic modeling in hormone receptor positive breast cancer is possible using the computational approach presented here. They also show that the addition of tumor heterogeneity data improved their prognostic model.

FOXM1 contributes to treatment failure in acute myeloid leukemia

Acute myeloid leukemia (AML) patients with NPM1 mutations demonstrate a superior response to standard chemotherapy treatment. Our previous work has shown that these favorable outcomes are linked to the cytoplasmic relocalization and inactivation of FOXM1 driven by mutated NPM1. Here, we went on to confirm the important role of FOXM1 in increased chemoresistance in AML. …

FOXM1 contributes to treatment failure in acute myeloid leukemia Read More »

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

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.

A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade

Evidence from mouse chronic viral infection models suggests that CD8+T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression …

A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade Read More »

A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma

Abstract We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified …

A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma Read More »