Consistent with previous studies (17, 25, 26), differentially gene expression analysis showed that BrMs had dramatically decreased cytotoxicity (CD8A, PRF1, GZMA, GZMB, GZMK, IFNG), chemokine (CXCL9, CXCL11, CXCL13, CCL5, CCL19, CCL21), proinflammatory cytokine (IL-6), immunoinhibitors (CTLA-4, LAG3, TIGIT) and immunocostimulators (CD28, ICOS, TNFSF13B), compared with primary lung cancers (Fig. 5A-F and Supplemental Figure S4), suggesting a suppressed TIME in BrMs. Here, CD28 is linked to lung cancer.