Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme InhibitorsReport as inadecuate




Pediatric Primitive Neuroectodermal Tumors of the Central Nervous System Differentially Express Granzyme Inhibitors - Download this document for free, or read online. Document in PDF available to download.

Background

Central nervous system CNS primitive neuroectodermal tumors PNETs are malignant primary brain tumors that occur in young infants. Using current standard therapy, up to 80% of the children still dies from recurrent disease. Cellular immunotherapy might be key to improve overall survival. To achieve efficient killing of tumor cells, however, immunotherapy has to overcome cancer-associated strategies to evade the cytotoxic immune response. Whether CNS-PNETs can evade the immune response remains unknown.

Methods

We examined by immunohistochemistry the immune response and immune evasion strategies in pediatric CNS-PNETs.

Results

Here, we show that CD4+, CD8+, γδ-T-cells, and Tregs can infiltrate pediatric CNS-PNETs, although the activation status of cytotoxic cells is variable. Pediatric CNS-PNETs evade immune recognition by downregulating cell surface MHC-I and CD1d expression. Intriguingly, expression of SERPINB9, SERPINB1, and SERPINB4 is acquired during tumorigenesis in 29%, 29%, and 57% of the tumors, respectively.

Conclusion

We show for the first time that brain tumors express direct granzyme inhibitors serpins as a potential mechanism to overcome cellular cytotoxicity, which may have consequences for cellular immunotherapy.



Author: Jeroen F. Vermeulen, Wim van Hecke, Wim G. M. Spliet, José Villacorta Hidalgo, Paul Fisch, Roel Broekhuizen, Niels Bovenschen

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents