TIMP1 mediates brain metastasis in a CD8+ T cell-dependent manner. Supplementary Figure 5 shows additional data corresponding to Figure 4.

Overall survival according to TIMP1 in the CSF. Overall survival of brain metastasis patients with different primary tumors according to their levels of TIMP1 in the cerebrospinal fluid (CSF). The table contains information corresponding to Supplementary Figure 9B.

TIMP1 is a downstream target of STAT3 in brain metastasis-associated astrocytes. Supplementary Figure 3 shows additional data corresponding to Figure 3.

TIMP1 levels from ELISA applied to CSF from patient samples. Levels of TIMP1 in the blood or in the cerebrospinal fluid (CSF) of non-cancer patients and brain metastasis patients from different primary tumors. Immune Cluster is shown for patients in Figure 7N. The table contains information corresponding to Figure 7L, 7N and Supplementary Figure 9A,C-D.

TIMP1 through CD63 alters relevant properties of CD8+ T cells. Supplementary Figure 6 shows additional data corresponding to Figure 6.

Phosphoproteomic analysis of CD8+ T cells incubated with astrospheres conditioned medium. Results from phosphopeptides quantification of the LC-MS/MS analysis of CD8+ lymphocytes incubated with pSTAT3- (D1) and wt (D2) or cKOGFAP-Timp1 (D2KO) pSTAT3+ astrospheres conditioned medium. The table contains information corresponding to Figure 6K and Supplementary Figure 7A.

DEG cluster 3 brain metastasis-associated astrocytes. Differentially expressed genes (DEGs) found in cluster number 3 of brain metastasis associated-astrocytes. Significantly deregulated genes are highlighted. Red indicates upregulation and green indicates downregulation respect to tumor free condition. The table contains information corresponding to Figure 1D.

Statistics of multiple experimental arms from in vivo immunotherapy experiments. Unpaired two-tailed Student’s t-test of different comparisons between the following experimental conditions: IgG2, silibinin and immune checkpoint blockade (ICB) (Anti-PD1 plus Anti-CTLA4) alone or in combination with silibinin in mice intracardially injected with B16/F10-BrM cells. Unpaired two-tailed Student’s t-test of different comparisons between the following experimental conditions: IgG2, cKOGFAP-Timp1 and immune checkpoint blockade (ICB) (Anti-PD1 plus Anti-CTLA4) alone or in combination in mice intracardially injected with E0771-BrM cells. The table contains information corresponding to Figure 7C and Supplementary Figure 8L.

Human brain metastases evaluated for pERK1/2 regarding their immune cluster. Information regarding multiplex of immune cells in human brain metastasis samples used for assessing pERK1/2 status in CD8+ T cells. The table contains information corresponding to Figure 6M.

TIMP1 binding to CD63 modulates kinase signaling in CD8+ T cells. Supplementary Figure 7 shows additional data corresponding to Figure 6.

Antibodies used for multiplex immunohistochemistry. Detailed information of antibodies used for multiplex.

STAT3-activation pathways in brain metastasis-associated astrocytes in human brain metastasis samples. Gene set enrichment analysis (GSEA) of STAT3-activation pathways in STAT3+ human brain metastasis associated-astrocytes. No significant alterations were found in cluster 3. The table contains information corresponding to Supplementary Figure 1P.

GSEA_comparision between cluster 3 and cluster 5 of brain metastasis-associated astrocytes in human brain metastasis samples. Gene set enrichment analysis (GSEA) of upregulated and downregulated signatures comparing cluster number 3 and number 5 of human brain metastasis associated-astrocytes. The table contains information corresponding to Figure 1I.

Human brain metastases evaluated with multiplex. Information regarding multiplex of immune cells and quantification of TIMP1 RNAScope staining in human brain metastasis samples. The table contains information corresponding to Figure 3G.

Analysis of potential interactions cluster 3-cluster 7. Top 25 interactions of potential secreted and potential membrane proteins in cluster number 3 and cluster number 7 of brain metastasis associated-astrocytes considering the experimentally determined interaction. The table contains information corresponding to Supplementary Figure 1M.

A combined immunotherapy targeting local immunosuppression provides superior control of brain metastasis. Supplementary Figure 8 shows additional data corresponding to Figure 7.

Patient-derived organotypic cultures (PDOC) treated with anti-TIMP1. Results from the Patient-derived organotypic brain cultures (PDOCs) of human brain metastasis treated with Anti-TIMP1 or Anti-TIMP1 and CD8 blockade. The table contains information corresponding to Figure 4F-G.

Patient-derived organotypic cultures as a surrogate to assess the potential of targeting local immunosuppression in brain metastasis. Supplementary Figure 9 shows additional data corresponding to Figure 7.

Heterogeneity within the brain metastasis microenvironment. Supplementary Figure 1 shows additional data corresponding to Figure 1.

Human brain metastasis samples analyzed with Chromium Fixed RNA Profiling. Clinical information of human brain metastasis samples included in Figure 1F-I.