Cancer discovery · 2026
Functionally active lymphoid aggregates correlate with improved prognosis in brain metastases.
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Nader Noor E, Glathar Alexandra R, Byrnes Elaine V, Joy Marion, Ge Tengziyi, Elliott Andrew, Jaehne Ryan, Layding Caroline J, Tatsuoka Curtis Mamoru, Sica Gabriel, Acharya Rajesh, Bao Riyue, Cillo Anthony R, Joon Aron Y, Kumar Swaminathan, Yanes Rami B, Wu Xiancheng, Solis Soto Luisa M, Arrechedera Claudio A, Tamegnon Auriole, Sanchez-Espiridion Beatriz, Tawbi Hussein A, Burton Elizabeth M, Davies Michael A, Pearce Thomas M, Burns Timothy F, Stabile Laura P, Zhang Xiaoran, Bruno Tullia C
Аннотация
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.