Institute of Biomedical Sciences

Title

Identification and Characterization of Pediatric Midline Glioma Specific Antigens: Wilms' Tumor in Diffuse Intrinsic Pontine Glioma

Poster Number

8

Document Type

Poster

Status

Graduate Student - Doctoral

Abstract Category

Cancer/Oncology

Keywords

Pediatric high grade glioma, Diffuse intrinsic pontine glioma, midline glioma, Wilm's tumor protein, Immunotherapy

Publication Date

Spring 2018

Abstract

Pediatric high grade gliomas (HGGs), especially those associated with the pons, known as diffuse intrinsic pontine gliomas (DIPGs) are deadly pediatric brain cancer that makes up 10-15% of all central nervous system (CNS) tumors in children. Its anatomical location and infiltrative nature makes it one of the most challenging tumors to treat. Immunotherapy is a technique that is gaining more interest in CNS tumors. Identification of tumor associated antigens is one of many requirements in developing an effective immunotherapy. Wilms’ tumor protein (WT1) has been ranked number 1 cancer immunotherapy target by National Cancer Institute. Many types of solid tumors have been shown to express WT1 and it is being examined as one of potential immunotherapeutic targets. Here we validated WT1 as a potential tumor associated antigen in pediatric diffuse midline gliomas using formalin fixed paraffin embedded (FFPE) tumor and intra-patient healthy specimens, fresh frozen post-mortem tissues and patient-derived DIPG primary cell lines. Our immunohistochemistry (IHC) staining of patient FFPE specimens showed strong WT1 immunoreactivity in tumor compared to adjacent normal tissue. Western blot of tumor tissues and cell lines were performed to further validate WT1 levels in the tumors versus adjacent normal tissues. Tumors showed cytoplasmic expression of WT1, confirmed by immunofluorescent (IF) staining. In addition, H3.1K27M subtype gliomas showed weak to absent WT1 immunoreactivity compared to strong to moderate in H3.3K27M subtypes. Western blots also validated the differential expression of the protein. Our study suggests that WT1 is a potential target protein for pediatric midline glioma immunotherapy.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

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Identification and Characterization of Pediatric Midline Glioma Specific Antigens: Wilms' Tumor in Diffuse Intrinsic Pontine Glioma

Pediatric high grade gliomas (HGGs), especially those associated with the pons, known as diffuse intrinsic pontine gliomas (DIPGs) are deadly pediatric brain cancer that makes up 10-15% of all central nervous system (CNS) tumors in children. Its anatomical location and infiltrative nature makes it one of the most challenging tumors to treat. Immunotherapy is a technique that is gaining more interest in CNS tumors. Identification of tumor associated antigens is one of many requirements in developing an effective immunotherapy. Wilms’ tumor protein (WT1) has been ranked number 1 cancer immunotherapy target by National Cancer Institute. Many types of solid tumors have been shown to express WT1 and it is being examined as one of potential immunotherapeutic targets. Here we validated WT1 as a potential tumor associated antigen in pediatric diffuse midline gliomas using formalin fixed paraffin embedded (FFPE) tumor and intra-patient healthy specimens, fresh frozen post-mortem tissues and patient-derived DIPG primary cell lines. Our immunohistochemistry (IHC) staining of patient FFPE specimens showed strong WT1 immunoreactivity in tumor compared to adjacent normal tissue. Western blot of tumor tissues and cell lines were performed to further validate WT1 levels in the tumors versus adjacent normal tissues. Tumors showed cytoplasmic expression of WT1, confirmed by immunofluorescent (IF) staining. In addition, H3.1K27M subtype gliomas showed weak to absent WT1 immunoreactivity compared to strong to moderate in H3.3K27M subtypes. Western blots also validated the differential expression of the protein. Our study suggests that WT1 is a potential target protein for pediatric midline glioma immunotherapy.