# Defining the role of tumoral MHC Class I Expression in Mediating Colorectal Cancer Racial Disparities

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $597,046

## Abstract

PROJECT SUMMARY
Compared to Whites, African American/Blacks (AA/B) have a substantially higher (40-50%) colorectal cancer
(CRC) mortality rate that is a function of both higher incidence and lower survival rates. Our long-term goal is
to understand the differences in immune response that influence this disparity in CRC mortality. Emerging
studies suggest alterations in T cell presence and function in AA/B contribute to CRC disparities, and AA/B CRC
patients with low immune infiltrate have particularly poor outcomes. We have found that AA/B CRC patients have
disproportionally reduced tumoral MHC class I expression compared with White patients. As MHC class I is
critical for presentation of tumor antigens to CD8+ T cells, these results suggest a critical immune mediated
mechanism that drives the differences in survival times between AA/B and White patients. The objectives of
this project are to understand the mechanisms relevant to T cell alterations within the tumors of AA/B versus
White patients and to develop improved biomarkers and therapies to reduce CRC racial disparities. Our central
hypothesis is that reduced tumoral MHC class I expression drives T cell alterations to enhance tumoral immune
escape in CRC from AA/B patients compared with White patients. To test this hypothesis, we have developed
robust multispectral imaging capability for studying the relationship between MHC class I expression and CD8+
T cell frequency, localization, phenotype, and function. In parallel, we have developed an autologous humanized
CRC TIL-PDX mouse model, created with matched patient-derived tumor and tumor infiltrating T cells (TILs) to
investigate CRC disparities. This completely unique approach will be undertaken by a multi-disciplinary team,
which includes a surgeon-scientist with expertise in CRC oncology, a cancer immunologist, and a cancer
disparities basic researcher. In Aim 1, we will define CD8+ T cell biology in the context of tumoral MHC class I
loss in AA/B versus White CRC patients. We will perform both multispectral imaging of archival tumor samples
and phenotypical/ functional studies of fresh samples to define essential differences between AA/B and White
tumors. In Aim 2, we will evaluate whether TIL-PDX mice generated from AA/B versus White CRC tumors exhibit
differential T cell biology and anti-tumor immunity in the context of tumoral MHC class I expression. We expect
that the use of the CRC TIL-PDX mouse model will recapitulates a patients’ tumor immunity in a manner not
previously possible to determine the differences in immune mediated processes. In Aim 3, we will assess the
ability of IL-15 as a therapy to overcome AA/B tumoral MHC class I loss using a syngeneic CRC tumor-bearing
mice. The positive impact of this work will be an improved understanding of the differences in immune-mediated
mechanisms to understand disparities associated with CRC patient outcomes and to develop a therapeutic
approach to help AA/B CRC patients.

## Key facts

- **NIH application ID:** 10894892
- **Project number:** 5R01CA264525-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Ernest Ramsay Camp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $597,046
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894892

## Citation

> US National Institutes of Health, RePORTER application 10894892, Defining the role of tumoral MHC Class I Expression in Mediating Colorectal Cancer Racial Disparities (5R01CA264525-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10894892. Licensed CC0.

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