# Illuminating B7-H3 Protein Dimerization and Function

> **NIH NIH F32** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $71,062

## Abstract

SUMMARY/ABSTRACT
Understanding the protein-protein interactions (PPIs) between the B7-family of immune regulatory proteins and
their cognate binding partners on the T-cell have led to a new era in cancer treatment, where checkpoint blockade
by monoclonal antibodies inhibiting CTLA-4 and PD-1 on the T-cell has revolutionized immunotherapy. These
PPIs provide both stimulatory secondary signals to promote and sustain T cell responses, and they also
contribute to negative secondary signals that downregulate T cell responses. PD-L1, PD-L2, B7-H3, B7-H4 and
HHLA-2 can be expressed on non-hematopoetic cells and tumors, but the role of temporal, as well as, spatial
differences in ligand expression and their contributions to pathogenic and protective immune responses have
not been fully elucidated. Many B7 family members, similar to other families of cell surface signaling proteins,
are known to exist as dimers, related to their signaling state. Thus, characterization of B7 family interactions and
oligomerization is essential to understanding the molecular mechanisms by which they alter the cancer cell to
confer an oncogenic phenotype. From a candidate gene approach, an interesting and novel target protein is B7-
H3, a member of the B7-family, which is overexpressed on the surface of many solid tumors. This proposal aims
to develop a bioluminescence-based, sequential resonance energy transfer (BLI-SRET) reporter of PPIs that
can be used to define structural features that contribute to B7-H3 dimerization and oligomerization and determine
the mechanism of how these interactions promote cancer cell survival and immune evasion. In aim 1, I will
develop a BLI-SRET system which can distinguish dimeric or multimeric protein complexes in a spatiotemporal
manner. This system will allow us to understand how signals are integrated at a molecular level through protein
dimerization and oligomerization, and provide a platform to aid characterizing those interactions that contribute
to pathogenesis. In aim 2, I will test the hypothesis that defined regions of B7-H3 contribute to protein clustering
and that ablation of these interacting domains will disrupt protein function, both intracellularly and extracellularly,
through the complemented immune synapse. As each interacting domain may serve a different downstream
function, understanding the similar or different mechanisms that regulate B7-H3-driven tumorigenesis may better
enable pathway-specific targeting of therapeutics and improve our understanding of B7-H3 oligomerization and
how this relates to its function. The research proposed herein will support my training and development as an
independent and productive cancer biologist, allowing me to gain a greater understanding of assay development,
genetically encoded optical biosensors, and the application of these tools to understand complex biological
processes. Using the longstanding practical expertise and development of optical imaging agents in the Piwnica-
Worms ...

## Key facts

- **NIH application ID:** 10179335
- **Project number:** 5F32CA250323-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Margie Nicole Sutton
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $71,062
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179335

## Citation

> US National Institutes of Health, RePORTER application 10179335, Illuminating B7-H3 Protein Dimerization and Function (5F32CA250323-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10179335. Licensed CC0.

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