Elucidating the mechanistic connection between the elevated occurrence of EGFR mutation in Hispanic/Latinx lung adenocarcinoma patients

Hispanic/Latinx (H/L) patients with lung adenocarcinoma have higher rates of epidermal growth factor receptor (EGFR) mutation than those who identify as non-H/L White. Although the overall survival outcome of H/L patients is better than non-H/L White patients, the subset of H/L patients with EGFR mutations have poorer survival outcomes. Immunotherapy has improved survival outcomes for lung adenocarcinoma, but their role in EGFR-mutant lung adenocarcinoma has been underwhelming, as EGFR-mutant tumors are often associated with an immunosuppressive tumor microenvironment and non-response to immunotherapy. Understanding how EGFR mutations and race/ethnicity shape the tumor immune microenvironment is critical to close gaps in health disparities. To address this, we utilized spatial transcriptomics (Visium HD) on lung adenocarcinoma patients from H/L and non-H/L patients stratified by EGFR status and sex (n=4 per group, n=24 total) to characterize spatial patterns of immune infiltration, immune cell composition, and changes to signaling pathways within the tumor-immune microenvironment. To validate and extend these findings to a larger population, bulk RNA-seq data (n=237) from a diverse cohort will be used to quantify immune-cell composition via cell deconvolution (CIBERSORT). In addition, associations between EGFR mutational status, race/ethnicity, and clinical variables including survival, smoking history, and therapy response are also considered. We hypothesize that EGFR-mutant tumors in H/L patients display distinct spatially organized immune-suppressive, resulting in the observed poorer survival outcomes. Taken together, this work integrates spatial and bulk transcriptomic approaches with EMR chart records to uncover mechanistic, race/ethnicity-specific immune features associated with EGFR mutation prevalence in H/L lung adenocarcinoma patients, with the goal of bridging the gaps in health outcomes.