CD47 performs a vital function in cancer therapy by binding to different SIRPα, thrombospondin 1, and integrin. However, its role in tumor immunity and its correlation with prognosis among many cancer types remain unknown. The raw mRNA expression data of CD47 in cancer patients was downloaded from TCGA and GTEx datasets. The protein expression of CD47 was detected using a microarray. Kaplan Meier analysis and forest plot were performed to compare the effects of high and low expression of CD47 on overall survival in different cancers. In addition, the correlations between CD47 expression and immune cell infiltration, stromal components, immune checkpoint genes, tumor mutational burden (TMB), and microsatellite instability (MSI) were analyzed from the public database. The gene function was determined by Gene Set Enrichment Analysis (GSEA). The expressions of CD47 in CHOL, COAD, ESCA, HNSC, KIRC, STAD, and THCA were higher compared with normal tissues. Elevated expression of CD47 predicted poor prognosis in ACC, KICH, KIRP, LGG, PAAD and UCEC. CD47 expression was strongly associated with immune infiltrating cells among KICH, KIRP, LGG, and PAAD. In addition, significant positive correlations with most immune checkpoint genes including PDCD 1 (PD-1), CD274 (PD-L1), CTLA4 in BLCA, DLBC, KICH, KIRC, LUAD, LUSC, PAAD, PCPG, SKCM, STAD, UCEC, and UVM was noted for the expression of CD47. GSEA analysis demonstrated that CD47 was a key regulator in metabolism-related pathways. These findings provide novel evidence that CD47 could be utilized as a promising prognostic biomarker and combination treatment target in various cancers.

The incidence of brain metastases (BrM) has become a growing concern recently. It is a common and often fatal manifestation in the brain during the end-stage of many extracranial primary tumors. Increasing BrM diagnoses can be attributed to improvements in primary tumor treatments, which have extended patients’ lifetime, and allowed for earlier and more efficient detection of brain lesions. Currently, therapies for BrM encompass systemic chemotherapy, targeted therapy, and immunotherapy. Systemic chemotherapy regimens are controversial due to their associated side effects and limited efficacy. Targeted and immunotherapies have garnered significant attention in the medical field: they target specific molecular sites and modulate specific cellular components. However, multiple difficulties such as drug resistance and low permeability of the blood-brain barrier (BBB) remain significant challenges. Thus, there is an urgent need for novel therapies. Brain microenvironments consist of cellular components including immune cells, neurons, endothelial cells as well as molecular components like metal ions, nutrient molecules. Recent research indicates that malignant tumor cells can manipulate the brain microenvironment to change the anti-tumoral to a pro-tumoral microenvironment, both before, during, and after BrM. This review compares the characteristics of the brain microenvironment in BrM with those in other sites or primary tumors. Furthermore, it evaluates the preclinical and clinical studies of microenvironment-targeted therapies for BrM. These therapies, due to their diversity, are expected to overcome drug resistance or low permeability of the BBB with low side effects and high specificity. This will ultimately lead to improved outcomes for patients with secondary brain tumors.