Resumen de Pediatric medulloblastoma express immune checkpoint B7-H3
S. Li, G. C. Poolen, L. C. van Vliet, J. G. Schipper, R. Broekhuizen, M. Monnikhof, W. Van Hecke, J. F. Vermeulen, N. Bovenschen
Purpose Medulloblastomas (MB) are highly malignant brain tumors that predominantly occur in young infants. Immunotherapy to boost the immune system is emerging as a novel promising approach, but is often hampered by inhibitory immune checkpoints. In the present study, we have studied immune checkpoint B7-H3 expression in a tissue cohort of human pediatric MB.
Methods Expression of B7-H3 was detected by immunohistochemistry and classified via B7-H3 staining intensity and percentage of B7-H3 positive tumor cells. Subsequently, B7-H3 protein expression was distinguished in MB molecular subtypes and correlated to immune cell infiltrates, patient characteristics, and survival.
Results B7-H3 protein expression was found in 23 out of 24 (96%) human pediatric MB cases and in 17 out of 24 (71%) MB cases > 25% of tumor cells had any level of B7-H3 expression. B7-H3 protein expression was more frequent on Group-4 MB as compared with other molecular subtypes (p = 0.02). Tumors with high B7-H3 expression showed less influx of γδT cells (p = 0.002) and CD3+ T cells (p = 0.041).
Conclusion Immune checkpoint B7-H3 is differentially expressed by the large majority of pediatric MB. This further warrants the development of novel B7-H3-directed (immuno)therapeutic methods for children with incurable, metastatic, or chemo-resistant MB.
