Evaluation of immunosignature profile in medulloblastoma

Email Principal Investigator
Completed
Specimen
Medulloblastoma
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Mateusz Koptyra

Children’s Hospital of Philadelphia
Philadelphia, PA, USA

CBTN Samples Used

38

CBTN Participants

38

CBTN Samples

CBTN Data Used

Backer

Arizona State University

Sanford Burnham Prebys Medical Discovery Institute

Completed

About this

Project

Medulloblastoma is the most common malignant pediatric brain tumor. Current therapies consist of surgical resection, whole brain or spinal cord radiation or aggressive chemotherapy. While five year survival in pediatric patients rates at 60-70%, survivors face neurological, intellectual, and physiological deficits due to the toxic effects of therapies on developing brain. Nevertheless, understanding medulloblastoma biology has dramatically increased over past 10 years. Advances in genetics and genomics allowed to stratify molecularly distinct tumor groups. Current, established consensus defines four main subgroups of medulloblastoma: WNT, HH, group 3 and group 4. Further investigations identify subgroups within subgroup and find significant differences in risk stratification, prognosis and therapeutic options for disease subtypes. While non-metastatic WNT subgroup patients have excellent survival rates (>90%), SHH subgroup patients harboring TP53 mutation and Group 3 patients with MYC amplifications belong to high risk patients of low survival rates (<50%). At the same time, targeted therapeutic options are in clinical phase of evaluation for SHH medulloblastoma. Current methods used for medulloblastoma profiling consist of mixed molecular and immunohistological methods and can be cumbersome. Detailed tumor molecular characteristics require access to tumor tissue, which can be a challenge, especially in brain cancers. Therefore, there is an urgent need to develop noninvasive diagnostic tools, which could elucidate patient’s clinical stratification.

Over the past years, technologies have been developed that permit non-invasive analysis of the cancer genome using either circulating tumor cells in the blood or cell-free circulating tumor DNA. These technologies emerge for some cancer types, but sensitivity of these methods remains low and because of the blood-brain barrier may be challenging to utilize for brain tumors. Immune surveillance however, occurs continuously and it is sensitive to antigen profile changes, like to humoral immune response induced by cancer cells. Analysis of immune response patterns can be possible through immunosignature, which is a pattern obtained when circulating antibodies in blood are allowed to bind to a large microarray of randomized–sequence peptides affixed to solid surface. This non-invasive approach requires very minimal volumes of blood and presents very high sensitivity. Moreover, it was shown already that cancer induce distinguished immunological patterns depending on type and stage.

Ask The

Scientists

Ask the scientists

What are the goals of this project?

We propose to evaluate immunosignature analysis pattern as a potential diagnostic tool in the medulloblastoma patient’s stratification.

We propose to analyze immunosignature profiles for medulloblastoma samples and compare them with current subtype stratification consensus according to RNA profiling.

What is the impact of this project?

We expect that our work will bring essential insights into applicability of immunosignature assay in medulloblastoma tumor profiling and could potentially facilitate patients’ diagnostic and prognostic.

Why the CBTN request is important to this project?

The multi-institutional Children's Brain Tumor Network, which collects and maintains de-identified biospecimens in a biorepository, is an exceptional source of biological specimens.

Specimen Data

The Children's Brain Tumor Network contribute 28 blood samples, 10 plasma samples and RNAseq data for this project.