Pediatric medulloblastoma express immune checkpoint B7-H3.

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.

Indomethacin-induced changes in renal blood flow velocity waveform in premature infants investigated with color Doppler imaging.

Renal dysfunction has been recognized as an adverse effect of indomethacin treatment and is probably secondary to impairment of renal blood flow. We therefore evaluated renal artery blood flow velocity in 15 premature infants with a symptomatic ductus arteriosus before and during the first 12 hours after a single intravenous dose of 0.1 mg/kg of indomethacin. Renal artery blood flow velocity was measured serially by color-Doppler flow imaging and used as a qualitative measure of true renal blood flow. Indomethacin administration led to a sharp decrease in peak systolic flow velocity and temporal mean flow velocity of the renal artery. This effect was maximal at 10 minutes after indomethacin dosing; the flow velocities showed a slow recovery, reaching baseline values again at 2 hours after indomethacin dosing. We conclude that indomethacin can affect renal blood supply in the premature infant for a period of at least 1 hour after indomethacin treatment.

Effect of indomethacin on superior mesenteric artery blood flow velocity in preterm infants.

In 15 preterm infants with symptomatic patent ductus arteriosus, blood flow velocity changes in the superior mesenteric artery were investigated with Doppler ultrasound just before and during the first 12 hours after a single dose of indomethacin. Indomethacin administration led to an instantaneous decrease in all infants of temporal mean flow velocity in the superior mesenteric artery, which was maximal 10 minutes after administration of indomethacin, followed by a more sustained recovery, slightly greater than baseline values, 12 hours after indomethacin treatment. Simultaneously determined temporal mean flow velocity of the anterior cerebral artery, used as an indicator of changes in cerebral blood flow, had a similar pattern as in the mean flow velocity in the superior mesenteric artery (r = 0.49; p less than 0.001). Our data suggest that indomethacin lowered blood supply to the bowel, similar to its action on cerebral blood flow.