Immunogenomic profiling of lung adenocarcinoma reveals high-grade growth patterns are associated with an immunogenic tumor microenvironment

Lung cancer is the leading cause of cancer-related mortality in the United States. Lung adenocarcinoma (LUAD) is the most common subtype and the most epidemiologically and genetically heterogeneous. Pathologists have routinely observed phenotypic heterogeneity among LUAD primary tumors as reflected by distinct patterns of tumor growth. However, despite prior implications on the association of immune-genomic environment and prognosis, this information is not utilized clinically. Herein, applying multiplatform immune-genomic analysis, we investigate two distinct classification systems and demonstrate that high-grade patterns of growth are associated with a distinct immunogenic tumor microenvironment that is predicted with a favorable response to immunotherapy, a finding with growing importance in the era of adjuvant and neoadjuvant immunotherapy.