# T cells in neurofibroma pathogenesis and malignanttransformation

> **NIH NIH K08** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $184,256

## Abstract

PROJECT SUMMARY
This proposal describes a five-year plan to prepare Steven Rhodes MD, PhD for independence as a physician
scientist studying the immuno-oncologic interfaces of neurofibromatosis (NF1)-associated peripheral nerve
sheath tumor progression. Dr. Rhodes completed his MD, PhD training at the Indiana University Medical
Scientist Training Program. Upon completion of his Pediatrics residency, he matriculated to subspecialty training
in Pediatric Hematology-Oncology, where he joined the laboratory of Dr. Wade Clapp and generated novel
genetically engineered mouse models (GEMMs) recapitulating the progression of benign plexiform and
precancerous atypical neurofibromas to malignant peripheral nerve sheath tumor (MPNST), a devastating form
of sarcoma that is the leading cause of death in persons with NF1. These GEMMs provide a tractable platform
to study the role of the immune microenvironment in governing the evolution of tumors along the neurofibroma
to MPNST continuum. Leveraging these GEMMs and samples from human NF1 patients, Dr. Rhodes discovered
that precancerous atypical neurofibromas are heavily infiltrated by T cells and exhibit signatures of enhanced
immune surveillance. These findings led us to hypothesize that T cells play a key role in preventing the outgrowth
of malignant clones in these precancerous tumors. The aims of this research are to 1) Define at single cell
resolution the clonal heterogeneity and functional states of infiltrating T cells in mouse models that recapitulate
the malignant transformation of plexiform and atypical neurofibroma; 2) Dissect spatial interaction networks
between infiltrating T cells and neoplastic Schwann cells within native tumor samples from NF1 patients; and 3)
Establish the utility of immune checkpoint inhibition, via CTLA-4 antagonism, to forestall malignant transformation
by potentiating T cell mediated anti-tumor activity in pre-cancerous atypical neurofibroma.
Indiana University School of Medicine and the Herman B Wells Center for Pediatric Research provides an
exceptional training environment for Dr. Rhodes to develop his research laboratory. The Department of
Pediatrics has an exceptional track record of NIH funded research (currently 6th in the nation) and offers access
to all the necessary resources for Dr. Rhodes to carry out the proposed scope of work. Dr. Clapp (primary
research mentor) is the co-PI of an NCI funded Developmental and Hyperactive Ras Tumor SPORE, focused
on NF1-associtated tumors, and has an exceptional track record of training young physician scientists. Dr.
Rhodes has assembled a diverse panel of mentors that will allow him to develop new expertise in T cell biology,
immuno-oncology and single cell analytics that will serve to distinguish him from his primary mentor and other
investigators in his field. Importantly, uncovering the cellular and molecular mechanisms modulating the
progression of NF1-associated peripheral nerve sheath tumors will provide key insight i...

## Key facts

- **NIH application ID:** 10853141
- **Project number:** 5K08NS128266-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** STEVEN DAVID RHODES
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $184,256
- **Award type:** 5
- **Project period:** 2022-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10853141

## Citation

> US National Institutes of Health, RePORTER application 10853141, T cells in neurofibroma pathogenesis and malignanttransformation (5K08NS128266-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10853141. Licensed CC0.

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