Journal Article DKFZ-2018-00207

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

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2018
Landes Bioscience Austin, Tex.

OncoImmunology 7(3), e1398877 - () [10.1080/2162402X.2017.1398877]
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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.

Classification:

Contributing Institute(s):
  1. B062 Pädiatrische Neuroonkologie (B062)
  2. DKTK Heidelberg (L101)
Research Program(s):
  1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2018
Database coverage:
Medline ; BIOSIS Previews ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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 Record created 2018-03-02, last modified 2024-02-29


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