Novel insights into the biology of brain metastasis

The incidence of brain metastases is on the rise due to improved cancer treatments, affecting patient morbidity and survival rates. Despite therapeutic advancements, treating brain metastases remains challenging due to the blood-brain barrier limitations. Understanding the unique biological and immunological characteristics of brain metastases is crucial for developing targeted therapies. Bioinformatics and data analysis play a key role in identifying molecular signatures and expression patterns related to brain metastasis.
To address these challenges, we performed comparative analysis of brain metastases from lung adenocarcinoma (BM-LUAD) and breast cancer (BM-BC). We found differences in immune response, higher immune infiltration, and higher expression of immune checkpoint molecules in BM-LUAD. Through the analysis of matched-paired samples, we identified the molecular mechanisms and druggable targets in BM-LUAD and BM-BC. We additionally investigated differences in immune- and cancer-related genes in non-small cell lung cancer (NSCLC) patients who developed brain metastasis and those who developed metastasis to other organ than the brain. We found differences in immune response in primary NSCLC samples in relation to subsequent brain-specific metastasis. Spatial profiling revealed specific organization of immune cells across the tissue.
Furthermore, we explored the association between gut microbiota, inflammatory immune markers, white blood cell counts, and risk of cancer development. We found a positive association between gut microbiota, higher SII levels, and higher lymphocyte and granulocyte counts, contributing to an increased risk of lung cancer development.