Introduction: Glioblastoma multiforme (GBM) is a fast growing, malignant primary brain tumor that occurs most frequently in adults and accounts for approximately 15% of all brain tumors. With a median survival time of less than two years, there is an immediate need for new and improved GBM therapies. The cellular membrane protein CD47 has been shown to inhibit phagocytic clearance of cancer cells in ovarian cancer, acute myeloid leukemia, non-Hodgkin’s lymphoma, and bladder cancer [1]. In this study the authors report gene expression of CD47 in human GBM in an effort to demonstrate the potential for therapeutic intervention at this target.

Methods: The Cancer Genome Atlas GBM data was accessed through the UCSC Cancer Genomics Browser, and gene expression data were collected and analyzed [2]. Samples were divided into two groups corresponding to high CD47 expression and low CD47 expression.

Results: The expression pattern of CD47 in 558 TCGA samples demonstrated an elevated level of CD47 gene expression in a number of cases (Fig. 1). The Kaplan-Meier survival curve depicts survival in the low CD47 group compared with the high CD47 group (Fig. 2).

Conclusions: Overexpression of CD47 on tumor cells has been shown to participate in the inhibition of phagocytosis in human malignancies. In addition, treatments that target CD47 to block its activity have demonstrated anticancerous efficacy by enabling phagocytosis of tumor cells in preclinical models of other cancers. CD47 may therefore serve as an attractive target of future GBM therapies.

Patient Care: Identification of therapeutic targets to facilitate the development of improved therapies for GBM will advance knowledge of GBM oncogenesis and treatment.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of CD47 expression in GBM. 2) Discuss, in small groups, the role of CD47 in GBM resistance to phagocytic clearance. 3) Identify an effective treatment to overcome the CD47-mediated evasion of phagocytosis in tumor cells.

References: [1] Chao MP, Weissman IL, Majeti R. The CD47-SIRPa Pathway in Cancer Immune Evasion and Potential Therapeutic Implications. Curr Opin Immunol. 2012 April ; 24(2): 225–232. [2] Zhu J, Sanborn JZ, Benz S, Szeto C, Hsu F, Kuhn RM, Karolchik D, Archie J, Lenburg ME, Esserman LJ, et al. The UCSC Cancer Genomics Browser. Nat. Methods 2009;6:239-240.