Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma

Abstract: Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Efficient killing of tumor cells using immunotherapy requires to overcome cancer-associated strategies to evade cytotoxic immune responses. Here, we examined the immune response and immune evasion strategies in pediatric medulloblastomas. Cytotoxic T-cells, infiltrating medulloblastomas with variable activation status, showed no correlation with overall survival of the patients. We found limited numbers of PD1+ T-cells and complete absence of PD-L1 on medulloblastomas. Medulloblastomas downregulated immune recognition molecules MHC-I and CD1 d. Intriguingly, expression of granzyme inhibitors SERPINB1 and SERPINB4 was acquired in 23% and 50% of the tumors, respectively. Concluding, pediatric medulloblastomas exploit multiple immune evasion strategies to overcome immune surveillance. Absence of PD-L1 expression in medulloblastoma suggest limited or no added value for immunotherapy with PD1/PD-L1 blockers

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
OncoImmunology. - 7, 3 (2018) , e1398877, ISSN: 2162-402X

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2019
Creator
Vermeulen, Jeroen F.
Hecke, Wim van
Adriaansen, Elisabeth J. M.
Jansen, Mieke K.
Bouma, Rianne G.
Villacorta Hidalgo, Jose Alberto
Fisch, Paul
Broekhuizen, Roel
Spliet, Wim G. M.
Kool, Marcel
Bovenschen, Niels

DOI
10.1080/2162402x.2017.1398877
URN
urn:nbn:de:bsz:25-freidok-1446011
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
25.03.2025, 1:45 PM CET

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Associated

Time of origin

  • 2019

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