A novel computer-assisted tool for 3D imaging of programmed death-ligand 1 expression in immunofluorescence-stained and optically cleared breast cancer specimens

• Published in: BMC cancer Vol. 24; no. 1; pp. 121 - 11
• Main Authors: Lee, Yi-Hsuan, Huang, Chung-Yen, Hsieh, Yu-Han, Yang, Chia-Hung, Hung, Yu-Ling, Chen, Yung-An, Lin, Yu-Chieh, Lin, Ching-Hung, Lee, Jih-Hsiang, Wang, Ming-Yang, Kuo, Wen-Hung, Lin, Yen-Yin, Lu, Yen-Shen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.01.2024; BioMed Central; BMC
• Subjects: Algorithms; Analysis; Antibodies; Apoptosis; B7-H1 Antigen; Breast cancer; Breast Neoplasms; Cancer immunotherapy; Care and treatment; Clinical significance; Coloring Agents; Computers; Death; Diagnosis; Female; Fluorescent antibody technique; Health aspects; Humans; Imaging, Three-Dimensional; Immune checkpoint; Immune Checkpoint Inhibitors; Immunofluorescence; Immunofluorescence staining; Immunohistochemistry; Immunotherapy; International economic relations; Invoices; Ligands; Medical equipment and supplies industry; Medical research; Medical test kit industry; Medicine, Experimental; Optical clearing; Patient outcomes; Patients; PD-1 protein; PD-L1 protein; Programmed Cell Death 1 Receptor; Programmed death-ligand 1; Scientific equipment and supplies industry; Software; Spatial distribution; Standardization; Three dimensional imaging; Taiwan; Canada; United States; United States > US; Immunofluorescence staining; Breast cancer; Optical clearing; Programmed death-ligand 1; Three-dimensional imaging
• DOI: 10.1186/s12885-023-11748-8
• ISSN: 1471-2407

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are the two most common immune checkpoints targeted in triple-negative breast cancer (BC). Refining patient selection for immunotherapy is non-trivial and finding an appropriate digital pathology framework for spatial analysis of theranostic biomarkers for PD-1/PD-L1 inhibitors remains an unmet clinical need. We describe a novel computer-assisted tool for three-dimensional (3D) imaging of PD-L1 expression in immunofluorescence-stained and optically cleared BC specimens (n = 20). The proposed 3D framework appeared to be feasible and showed a high overall agreement with traditional, clinical-grade two-dimensional (2D) staining techniques. Additionally, the results obtained for automated immune cell detection and analysis of PD-L1 expression were satisfactory. The spatial distribution of PD-L1 expression was heterogeneous across various BC tissue layers in the 3D space. Notably, there were six cases (30%) wherein PD-L1 expression levels along different layers crossed the 1% threshold for admitting patients to PD-1/PD-L1 inhibitors. The average PD-L1 expression in 3D space was different from that of traditional immunohistochemistry (IHC) in eight cases (40%). Pending further standardization and optimization, we expect that our technology will become a valuable addition for assessing PD-L1 expression in patients with BC. Via a single round of immunofluorescence imaging, our approach may provide a considerable improvement in patient stratification for cancer immunotherapy as compared with standard techniques.