Bsbm-06 unraveling the immune microenvironment of brain metastasis from lung adenocarcinoma

Abstract Brain metastasis (BM) is a common complication of advanced lung adenocarcinoma (LUAD) and is associated with significantly poor prognosis and reduced quality of life. The immune system plays a critical role in the development and progression of BM, as well as in response to therapy. Herein, we used Next-Generation Sequencing (NGS) and array technologies to elucidate the immune landscape of LUAD-BM. NGS data from BM and primary tumors (T): RNA-Seq (n=24; 13 BM and 11 T), microarray (n=140; 63 BM and 77 T) were used for quantifying the immune cell fractions by CIBERSORT. Additionally, single-cell (scRNA-seq) data (n=57,774 cells; 23 BM samples) were used for data validation. Results showed that resting memory T CD4 comprised the largest cellular fraction (17.4%) of the total immune cells in BM. Furthermore, the fraction of resting dendritic cells (DC) was lower in BM vs. T, while the neutrophil fraction was higher (p<0.05). ScRNA-seq confirmed the presence of DC and neutrophils in BM, identifying multiple subsets of DC (cDC1, cDC2/MoDC, and DC3) that are highly conserved across solid human cancers with cDC2/MoDC as the most frequent subpopulation among dendritic cells. Therefore, our results show a different immune profile between BM and primary LUAD. The immune environment of LUAD-BM is highly suppressed, accompanied by enriched T cell subpopulations predicted as immature T cells. The identification of cDC2/MoDC subpopulations in LUAD-BM replicates the findings observed in BM from melanoma patients. It has been shown that cDC2 can interact with CD4+ T cells to promote anti-tumor immune responses. Our findings elucidate the profiles of LUAD-BM immune microenvironment, comprehensively identifying specific immune subpopulations with important roles in the establishment and progression of BM from LUAD.