# Investigating mechanisms underscoring dichotomous T cell responses between medulloblastoma subgroups

> **NIH NIH F32** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2021 · $47,563

## Abstract

PROJECT SUMMARY/ABSTRACT (30 lines of text):
Medulloblastomas are one of the most common childhood brain tumors and are comprised of several histological
and molecularly distinct subtypes based on genetic, clinical, and prognostic factors. Transcriptional profiling has
subsequently identified four subgroups which include wingless/integrated (WNT)-activated, sonic hedgehog
(SHH)-activated, Group 3, and Group 4. Each subtype differs in clinical prognoses, in which WNT tumors have
best outcomes, SHH and Group 4 have intermediate prognoses, and Group 3 have the worst outcomes.
Standard therapeutic treatment of these tumors includes surgery, radiation and chemotherapy. However, long-
term side-effects often result in negative side-effects for patients, as noted through global reductions in
physiological, psychological, and economic welfare of patients. Immunotherapy, given the success in adult
tumors, is an attractive option as it may impart similar therapeutic success with potentially diminished adverse
side-effects. Immunotherapies hinge on the relative abundance and cytolytic effector capacity of CD8+ T cells.
Activation of these cells is dependent on both the immunogenicity of tumors and on priming by competent
migratory antigen presenting cells. Once migrated to tumors, relative antitumor success of T cells is dictated by
the capacity of cells to overcome the immunosuppressive tumor environment. T cells must also resist T cell
exhaustion which results from the persistent antigenic environment of tumors. Establishment and propagation of
this exhaustive cell fate decision has been demonstrated to be intimately tied to epigenetics. Our preliminary
data shows striking differences in PD1hiCD8+ T cells between Group 3 and SHH preclinical tumor models, in
which there is high infiltration of these T cells into Group 3 tumors and low infiltration into SHH tumors.
Conversely, we have observed significantly higher infiltration of PD1hiCD8+ T cells in the tumor-draining lymph
nodes of SHH tumors expressing N-Myc as compared to Group 3 tumor-draining lymph nodes. Taken together,
this dichotomy may underscore differential therapeutic responsiveness, particularly in the presence of checkpoint
blockade. In this proposal, we aim to investigate both tumor immunogenicity and T cell dysfunction as potential
mechanisms underscoring these dichotomous T cell responses between medulloblastoma subgroups. In
particular, we will examine the inherent immunogenicity of tumors in vivo and determine if established epigenetic
mechanisms of T cell exhaustion impacts the abundance and therapeutic responsiveness of T cells in Group 3
and SHH medulloblastomas. The completion of these aims will add to a deeper understanding of the underlying
biological differences between the clinical outcomes of medulloblastoma subgroups, as well as inform studies
aimed at enhancing the efficacy of T cell-based therapeutics in medulloblastoma. Furthermore, the techniques
outlined in this proposal w...

## Key facts

- **NIH application ID:** 10143613
- **Project number:** 1F32CA250155-01A1
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Shannon Boi
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $47,563
- **Award type:** 1
- **Project period:** 2021-01-01 → 2021-08-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143613

## Citation

> US National Institutes of Health, RePORTER application 10143613, Investigating mechanisms underscoring dichotomous T cell responses between medulloblastoma subgroups (1F32CA250155-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10143613. Licensed CC0.

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