Teacher-student collaborated multiple instance learning for pan-cancer PDL1 expression prediction from histopathology slides

ABSTRACT Programmed cell death ligand 1 (PDL1), as an important biomarker, is quantified by immunohistochemistry with few established histopathological patterns. Deep learning aids in histopathological assessment, yet heterogeneity and lacking spatially resolved annotations challenge precise analysis. Here, we present a weakly supervised learning approach using bulk RNA sequencing for PDL1 expression prediction from hematoxylin and eosin (H&E) slides. Our methods, MILTS, extends multiple instance learning paradigm with the teacher-student framework, which assigns dynamic pseudo-labels for intra-slide heterogeneity and retrieves unlabeled instances using temporal ensemble model distillation. The approach, evaluated on 12,299 slides across 20 solid tumor types, achieves a weighted average AUC of 0.83 on fresh-frozen and 0.74 on formalin-fixed specimens for 9 tumors with PDL1 as an established biomarker. MILTS predicts PDL1 expression patterns, validated by immunohistochemistry on 20 slides, offering insights into histologies relevant to PDL1. This demonstrates the potential of deep learning in identifying diverse histological patterns for molecular changes from H&E images.