# Tumor and Host Immune signatures associated with health disparities in outcomes following GD2 immunotherapy in neuroblastoma

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $576,659

## Abstract

PROJECT SUMMARY
Neuroblastoma (NB) is the most common extracranial solid tumor of childhood that leads to a disproportionate
number of childhood cancer deaths and an even more disproportionate death rate in Black children. Despite the
addition of GD2 antibody (dinutuximab) immunotherapy, disparities in outcome remain, suggesting racial/ethnic
differences in immunity may contribute to NB patient health inequity. While social determinants of health (SDOH)
like household poverty have been found to play a role in outcome disparities for high risk NB, biologic factors
contributing to racial disparities in NB survival are largely unexplored.
Dinutuximab requires innate effector immune cells to enact antibody dependent cellular cytotoxicity (ADCC) for
efficacy. We have found that the presence of circulating cytotoxic natural killer (NK) cells is associated with
objective responses to dinutuximab in a phase I trial for patients with relapsed NB. Furthermore, innate immune
cell infiltrates in high-risk NB tumors may differ between Black and non-Hispanic White patients, with Black
patients having more exhausted tumor-resident NK cells. We therefore hypothesize that racial differences in
high-risk NB patient innate immune cell landscapes, due to genomic ancestry and SDOH exposures, contribute
to outcome disparities following GD2 immunotherapy.
A Children’s Oncology Group randomized phase III trial will evaluate whether the addition of dinutuximab to
induction chemotherapy (“induction chemoimmunotherapy”) will improve event-free survival (EFS) and overall
survival (OS) for newly diagnosed high-risk NB patients. The trial includes a novel embedded health equity
substudy to capture parent-reported race and SDOH. The goal of this proposal is to utilize trial-derived biologic
samples to: i) Perform tumor based single cell genomic, proteomic, and functional investigations before and after
chemoimmunotherapy to determine tumor immune microenvironment markers influencing EFS/OS, ii) Perform
immunophenotyping and functional assays to define peripheral host immune markers influencing EFS/OS, and
iii) Explore the associations between tumor and host immune landscapes and parent-reported race, adverse
SDOH, child DNA-based genetic ancestry, and clinical outcomes.
At the conclusion of this project, we will have defined immune biomarkers of EFS/OS across all patients and
evaluated immune biomarkers of poor EFS/OS to see if they are enriched in Black children and/or children
exposed to adverse SDOH. Importantly, these findings may identify new immunotherapeutic targets for specific
patient populations to improve survival and achieve health equity in patients with high-risk neuroblastoma.

## Key facts

- **NIH application ID:** 10980735
- **Project number:** 1R01CA285566-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Kavita Madhav Dhodapkar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $576,659
- **Award type:** 1
- **Project period:** 2024-07-02 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980735

## Citation

> US National Institutes of Health, RePORTER application 10980735, Tumor and Host Immune signatures associated with health disparities in outcomes following GD2 immunotherapy in neuroblastoma (1R01CA285566-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10980735. Licensed CC0.

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