Summary
Brain metastases (BrM) are the most common cancers in the brain. We performed transcriptome-wide gene expression profiling combined with spatial immune cell profiling to characterize the tumor immune microenvironment in BrM from different primary tumors. We found that BrM from lung carcinoma and malignant melanoma showed overall higher immune cell infiltration as compared to BrM from breast carcinoma. RNA sequencing-based immune cell deconvolution revealed gene expression signatures indicative of tertiary lymphoid structures (TLS) in subsets of BrM, mostly from lung cancer and melanoma. This finding was corroborated by multiplex immunofluorescence staining of immune cells in BrM tissue sections. Detection of TLS signatures was more common in treatment-naïve BrM and associated with prolonged survival after BrM diagnosis in lung cancer patients. Our findings highlight the cellular diversity of the tumor immune microenvironment in BrM of different cancer types and suggest a role of TLS formation for BrM patient outcome.
Competing Interest Statement
SSM, YR, IH, LM, JF, SS, JM, KK, HW, GR, KHP, BB declare no conflict of interest. VM: research support from Novartis, Roche, Seagen, Genentech, Astra Zeneca and honoraria for lectures from Astra Zeneca, arsTempi, Daiichi-Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Lilly, Medscape, Gilead, Pierre Fabre, iMED Institute as well as consultancy honoraria from Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Seagen, Gilead, Stemline. AB: research support from Daiichi Sankyo, Roche and honoraria for lectures, consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo, AstraZeneca, CeCaVa, Seagen, Alexion, Servier as well as travel support from Roche, Amgen and AbbVie. TF: received honoraria from Onkowissen, FOMF, Medconcept and travel support from Roche. DS: has offered consultation to Philogen, lnFlarX, Neracare, Merck Sharp & Dohme, Novartis, Bristol Myers Squibb, Pfizer, Pierre Fabre, Replimune, SunPharma, Daiichi Sanyo, Astra Zeneca, IQVIA, LabCorp, UltimoVacs, Seagen, Immunocore, Immatics, BioNTech, PamGene, BioAlta, Regeneron, Agenus, Erasca, Formycon, NoviGenix, CureVac, and Sanofi and has received research grants from Amgen, BMS, MSD, and Pfizer.
Data availability
Sequencing data were deposited in the European Genome-Phenome Archive (EGA) under accession EGAS50000000563. The nanostring data of the Rubio-Perez et al. (2021) BrM cohort24 used for Figure 4E and Figure S6A were retrieved from the publicly available Gene Expression Omnibus (GEO) database under accession code GSE159407.
