# Characterizing the immune infiltrate in muscle-invasive urothelial carcinoma

> **NIH NIH K08** · OHIO STATE UNIVERSITY · 2024 · $273,561

## Abstract

Project Summary
Urothelial carcinoma is a common, aggressive, morbid, and understudied disease. Many patients are not cured
with the current standard of care for localized muscle-invasive urothelial carcinoma, which is neoadjuvant
combination cisplatin-based chemotherapy followed by radical cystectomy. But overall survival is significantly
longer in patients who obtain a pathologic complete response to neoadjuvant chemotherapy, suggesting that
intensification of systemic therapy will improve survival. It is critical that we develop reliable predictive biomarkers
that can select patients that will or will not have a complete pathologic response to receive, respectively, either
chemotherapy or an intensified peri-operative regimen. Preliminary evidence in urothelial carcinoma and other
cancers suggests that infiltrating immune cells play a role in treatment response, but this has not been rigorously
studied in muscle-invasive urothelial carcinoma. In this study, we will interrogate pre- and post-treatment
samples from a completed, pivotal phase II clinical trial, harnessing our expertise in spatial transcriptomics and
proteomics to interrogate differential gene and protein expression in tumor, immune, and stromal cells in
annotated tissue specimens before and after neoadjuvant chemotherapy with or without a checkpoint inhibitor.
Specifically, we will evaluate baseline CD8:FOXP3 ratio and responses to therapy (Aim 1), determine the effect
of neoadjuvant therapy on CD8:FOXP3 ratio (Aim 2), and leverage the full capacity of spatial
transcriptomic/proteomic assays to develop and evaluate the performance of novel predictive biomarkers of
response to neoadjuvant therapy (Aim 3). This study will result in predictive biomarkers while concurrently
profiling the immune infiltrate composition and how it is influenced by treatment. The ultimate goal is to design
rational combination or sequential peri-operative regimens for biomarker-driven clinical trials to improve patient
survival and cure rates. The project will provide the candidate, Katharine Collier, MD, MSc, MSE, MS, with
training in rigorous quantitative methods, cutting-edge spatial molecular analyses, and high-dimensional
biomarker development. The proposal capitalizes on Dr. Collier’s quantitative background in Chemical
Engineering, clinical training in Medical Oncology, and formal training in clinical trial design, while providing an
opportunity to gain additional skills and knowledge in multi-omics techniques and data analyses, preclinical
studies, leadership, presentations, and grant writing. Dr. Collier is committed long-term to improving outcomes
for patients with genitourinary cancers as a translational physician-scientist. Dr. Collier will be supported by an
experienced mentorship team (Amir Mortazavi, MD, Zihai Li, MD, PhD, Daniel Stover, MD, Steven Clinton, MD,
PhD), skilled collaborators, the rich academic environment of the Ohio State University Comprehensive Cancer
Center, and an invest...

## Key facts

- **NIH application ID:** 10880631
- **Project number:** 5K08CA277016-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Katharine A. Collier
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $273,561
- **Award type:** 5
- **Project period:** 2023-07-04 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880631

## Citation

> US National Institutes of Health, RePORTER application 10880631, Characterizing the immune infiltrate in muscle-invasive urothelial carcinoma (5K08CA277016-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10880631. Licensed CC0.

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