Brief Report: The Immune Profiles of the Molecular Subtypes of EGFR-Mutant Lung Adenocarcinomas in a Large Real-World Cohort

EGFR-mutant tumors with exon 19 deletions, L858R mutations, or exon 20 insertions were less likely to be PD-L1 high (TPS ≥ 50%) or TMB high (≥10 mut/MB) as compared to wild-type (WT) tumors. Among EGFR-mutant tumors, those with uncommon alterations in L861Q and G719X had greater rates of TMB high and TP53 co-mutations. • Utilizing bulk RNA sequencing data to characterize the immune tumor microenvironment (TME), exon 19 deletion and L858R mutation tumors were found to have lower median percent fractions of CD8+ T cells versus WT. However, a wide range of values for CD8+ T cells was observed and a subset of exon 19 deletion and L858R tumors had higher values comparable to WT. • Exon 19 deletion, L858R, and exon 20 insertion tumors were enriched with immunosuppressive M2 macrophages and neutrophils as compared to WT. In contrast, L861Q and G719X tumors had levels of M2 macrophages similar to WT. • A small subset of EGFR-mutant tumors, particularly those with uncommon alterations, bear characteristics that may render them more immunogenic. Continued research is needed to evaluate biomarkers, including the specific subtype of EGFR, as predictors of immunotherapy response to better identify the small subgroup of patients with EGFR-mutant disease that benefit from checkpoint inhibitors.