Quantitative image analysis for CD8 score in lung small biopsies and cytology cell‐blocks

Abstract

Introduction Immunotherapy has shown promising results in non‐small cell lung cancer (NSCLC), for which tumour‐infiltrating cytotoxic (CD8+) T cells play a critical role. We investigated the utility of image analysis (IA) to quantify CD8+ T cells in a series of matched small biopsies and resections of NSCLC. Methods CD8 immunohistochemistry was performed on cell‐blocks (CB), core needle biopsies (CNB) and corresponding resections from primary NSCLCs. Slides were digitised using an Aperio AT2 scanner (Leica) and annotated by whole slide image (WSI) or fields of view occupied by tissue spots (TS). Quantitative IA was performed with a customised Aperio algorithm (Leica). CD8 scores (number of T cells with 1‐3+ staining/total area) were then compared. Results Forty‐four cases with CB or CNB material and a corresponding resection were analysed. Average CD8 score was determined in CB (7.67 WSI, 77.67 TS) and/or CNB (47.35 WSI, 325.67 TS), and corresponding resections (190.35 WSI, 336.58 TS). CD8 score concordance was highest (78.6%) for CNBs using WSI annotation. Overall, small biopsies (CB or CNB) correlated with the resection in 71.4% cases using WSI and 63.3% cases using TS annotation. IA performed better for low CD8 scores. Conclusions These findings show that CD8 density in NSCLC can be quantified by IA in small biopsies and cell blocks, achieving the best concordance using WSI scores. Discrepancies were attributed to values near the cut‐off and background detection of staining. These data warrant future studies with more cases and follow‐up data to further investigate the clinical utility of IA for CD8 analysis in NSCLC.

Effects of Propofol and Sevoflurane on Cellular Immune Function and Postoperative Complications in Patients with NSCLC Undergoing Surgery

“…Many studies have shown that CD8 + in ltrated in tumors plays an important role in anti-tumor immune response. The in ltration of CD8 + high-expressing T cells in tumors helps to improve the clinical outcome of cancers including NSCLC [23][24]. NK cells constitute the rst line of defense against microbial infections and cancer development.…”

Beyond PD‐L1: Assessment of LAG‐3 and other predictive biomarkers in non–small cell lung carcinoma

“…How the assessment of LAG-3 and other immunoregulators may vary on cytologic specimens remains largely unknown, whereas the use of cytology smears or cell blocks for the assessment of immune cell markers that are more abundant in tumor-associated stroma24 may not seem appropriate. Furthermore, although currently most of the clinical assessment of PD-L1 expression relies on a manual semiquantitative approach, computer-assisted quantitative analysis of PD-L1 expression and CD8 + tumor-infiltrating lymphocytes has been reported,37,38 and this has included the use of cytology specimens 39. Nevertheless, because of the increasing use of ICIs in oncology, for diagnostic surgical pathology and cytopathology, further research and clinical implementation of additional predictive biomarkers, including LAG-3, are yet to come.…”