Immunotherapy has revolutionized cancer treatment, yet predicting which patients will respond remains a major clinical challenge. Current predictive biomarkers, such as PD-L1 expression, have limited accuracy and fail to capture the complex interplay of cells within the tumor microenvironment. Digital histopathology, the analysis of digitized tissue slides, combined with artificial intelligence (AI), offers a novel approach to identify complex morphological patterns that could serve as more robust predictive biomarkers. Objective: A deep learning model, specifically a convolutional neural network (CNN), was trained on a large, multi-center cohort of digitized tumor slides from patients with non-small cell lung cancer who had received ICI therapy. The model was trained to identify subtle morphological features and the spatial arrangement of tumor cells and tumor-infiltrating lymphocytes. The model’s predictive performance was rigorously validated on an independent, held-out test cohort, and its performance was compared to the predictive accuracy of PD-L1 staining. The AI-powered model successfully predicted immunotherapy response with a high degree of accuracy, achieving an area under the receiver operating characteristic curve (AUC) of 0.88 in the validation cohort.
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