Functionally active lymphoid aggregates correlate with improved prognosis in brain metastases

B cells and their cellular neighborhoods, i.e., lymphoid aggregates (LAs) and tertiary lymphoid structures (TLS), have not been extensively studied in melanoma brain metastases (BM) or lung adenocarcinoma (LUAD) BM, despite their prognostic value and role in immunotherapeutic responses. In this study, we evaluated the prognostic benefit and heterogeneity of B cell infiltration and LA formation in more than 200 patients with melanoma-BM or LUAD-BM. We found that LAs were associated with increased intratumoral CD8+T cells in melanoma-BM compared with LUAD-BM. Moreover, the presence of LAs was associated with an increased survival benefit in patients with melanoma-BM but not in those with LUAD-BM. Despite lacking canonical TLS hallmarks, LAs in BM contained proliferating B and T cells with the potential for effector function. Our work has solidified the need for the mechanistic investigation of intracranial B cells and the immune neighborhoods in which they reside.