Pediatric medulloblastoma express immune checkpoint B7-H3

• S. Li ^[1] ; G. C. Poolen ^[1] ; L. C. van Vliet ^[1] ; J. G. Schipper ^[1] ; R. Broekhuizen ^[1] ; M. Monnikhof ^[1] ; W. Van Hecke ^[1] ; J. F. Vermeulen ^[1] ; N. Bovenschen ^[2]
  1. [1] Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
  2. [2] Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands Center for Translational Immunology, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 24, Nº. 6 (junio), 2022, págs. 1204-1208
• Idioma: inglés
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• Resumen

  • 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.