AUTHOR=Jiao Feng , Shang Zhanxian , Lu Hongmin , Chen Peilin , Chen Shiting , Xiao Jiayi , Zhang Fuchuang , Zhang Dadong , Lv Chunxin , Han Yuchen TITLE=A weakly supervised deep learning framework for automated PD-L1 expression analysis in lung cancer JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1540087 DOI=10.3389/fimmu.2025.1540087 ISSN=1664-3224 ABSTRACT=The growing application of immune checkpoint inhibitors (ICIs) in cancer immunotherapy has underscored the critical need for reliable methods to identify patient populations likely to respond to ICI treatments, particularly in lung cancer treatment. Currently, the tumor proportion score (TPS), a crucial biomarker for patient selection, relies on manual interpretation by pathologists, which often shows substantial variability and inconsistency. To address these challenges, we innovatively developed multi-instance learning for TPS (MiLT), an innovative artificial intelligence (AI)-powered tool that predicts TPS from whole slide images. Our approach leverages multiple instance learning (MIL), which significantly reduces the need for labor-intensive cell-level annotations while maintaining high accuracy. In comprehensive validation studies, MiLT demonstrated remarkable consistency with pathologist assessments (intraclass correlation coefficient = 0.960, 95% confidence interval = 0.950-0.971) and robust performance across both internal and external cohorts. This tool not only standardizes TPS evaluation but also adapts to various clinical standards and provides time-efficient predictions, potentially transforming routine pathological practice. By offering a reliable, AI-assisted solution, MiLT could significantly improve patient selection for immunotherapy and reduce inter-observer variability among pathologists. These promising results warrant further exploration in prospective clinical trials and suggest new possibilities for integrating advanced AI in pathological diagnostics. MiLT represents a significant step toward more precise and efficient cancer immunotherapy decision-making.