Classification of the Tumor Immune Microenvironment Using Machine-Learning-Based CD8 Immunophenotyping As a Potential Biomarker for Immunotherapy and TGF-β Blockade in Nonsmall Cell Lung Cancer

Background: The cellular composition of the tumor immune microenvironment (TIME) is a key contributor to the response of the tumor to immunotherapy. Transforming growth factor-beta (TGF-β) signaling is known to promote immune exclusion, where CD8+ T cells are in the surrounding stromal tissue but not within the tumor itself. To better identify patients with an immune-excluded phenotype, we developed two machine learning (ML) models to quantify CD8+ cell positivity and classify the immunophenotype of a histological cancer specimen.