Abstract 3023: B7 H3 and autophagy in medulloblastoma

B7-H3 and Autophagy in Medulloblastoma (MB) is the most common malignant pediatric brain tumor and we reported high expression of the immune checkpoint protein, B7-H3. We also showed that B7-H3 promotes exosome secretion, with a plausible cross-talk between exosomes and autophagy in tumor development. Autophagy promotes or suppresses tumorigenesis but its role in pediatric brain tumors has not be elucidated. As our recent research has shown, the elevated levels of B7-H3 in MB enhances exosome secretion that may regulate autophagy processes favoring tumorigenesis over tumor suppression. Therefore, the goal of this study is to investigate the relationship between B7-H3 and autophagy pathways in MB in efforts to improve treatment options and patient survival. Datamining studies conducted using MB patient datasets showed a negative correlation between B7-H3 and autophagy markers; Beclin1, LC3, and ATGs. Kaplan-Meier analysis further demonstrated an inverse relationship between autophagy markers and B7-H3 in the survival curves. Next, using human autophagy array, we observed significant reduction in the expression of Beclin1, LC3, and ATGs upon B7-H3 overexpression in D425 cells. In a separate experiment, we show that silencing B7-H3 using specific shRNA resulted in increased levels of LC3-II. Functional studies performed using FACs analyses and clonogenic assay on shB7-H3 treated- D425, UW228 cells revealed that inhibition of B7-H3 was associated with augmented apoptosis and reduction in colony formation, respectively. These results demonstrate the negative role of B7-H3 in MB autophagy regulation. Therefore, inhibition of B7-H3 may prove effective at promoting autophagy-mediated cell death in MB cells. Citation Format: Ayse E. Kesaf, Katherine Shishido, Kiran K. Velpula, Swapna Asuthkar. B7 H3 and autophagy in medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3023.