IMMU-27. Identification of prognostically relevant immune ecotypes in lung adenocarcinoma brain metastases

Abstract Brain metastases are a severe complication for lung adenocarcinoma patients. Immunotherapies build a promising treatment option, but there is still a limited understanding of the patient-individual immune cell composition within these brain metastases and its prognostic and predictive implications. We studied a clinically annotated cohort of n = 76 neurosurgically resected lung adenocarcinoma brain metastases for their infiltration by various immune cells, including T cells, B cells, plasmablasts, macrophages, and granulocytes, applying multiplexed imaging of whole slides and cell quantification by tissue cytometry. In addition, broad clinical data, matched bulk transcriptomes, and serum cytokine levels of patients were assessed for integrative analyses with the tissue immune cell quantities. Our analyses revealed the grouping of brain metastases into four cell-type integrative immune ecotypes, each characterized by a unique immune cell composition and infiltration rate. The immune ecotypes were associated with a distinct overall survival, independent of clinical prognostic variables in a multivariate model. Interestingly, a subgroup of brain metastases enriched for B cells, often spatially arranged with T cells and other specialized cell types in tertiary lymphoid structures, was especially linked to a favorable prognosis. Integrative analyses of bulk transcriptome data further enabled the identification of related gene expression signatures. Our current analyses assess the suitability of serum cytokines as surrogate markers for the brain metastases immune ecotypes, evaluating patient-matched samples. Together, our analyses advance the knowledge of lung adenocarcinoma immune landscapes in the brain metastatic niche and suggest characteristics that could translate to clinically applicable biomarkers in the future.