# Variation in tumor-associated immune profiles and colorectal cancer outcomes

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $645,534

## Abstract

Considerable variability in tumor-associated immune responses exists across racial/ethnic populations.
These variations may explain part of the observed disparities in response to cancer therapies, particularly
immunotherapy, and treatment outcomes. In colorectal cancer (CRC), the intensity and composition of tumor
infiltrating lymphocytes (TIL) are established prognostic and predictive indicators. However, factors
contributing to the diversity of TIL responses observed among CRCs remain largely unknown, and the
influence of race/ethnicity and genetic ancestry have been underexplored. In a recent study comparing CRCs
from African Americans and non-Hispanic Whites, differences in lymphocytic reactions were observed to
partially explain the survival disparity between the two groups. No data is available for other racial/ethnic
groups. Prior research has also been limited by relying solely on self-reported race/ethnicity, a significant
limitation. Studies show that self-report does not fully or accurately reflect the genetic diversity present in
admixed minority populations. We hypothesize that ancestral genetic architecture is important for shaping
immune-related determinants of CRC outcomes given the differential efficiency of immune function observed
across racial/ethnic groups. Studies in the genertically admixed Latinx population offer notable advantages
including a unique opportunity to simultaneously tease out the contributions of multiple ancestral backgrounds
(e.g. African, European, Indigenous American) to variability in immune function. Here, we will test the
hypothesis that genetic ancestry is independently associated with differences in tumor-associated T cell
profiles that contribute to CRC outcome disparities (i.e. observed across populations defined by ethnicity and
by genetic ancestry) using existing resources from the Hispanic Colorectal Cancer Study, the Puerto Rico
Biobank, the Total Cancer Care Protocol, and the Molecular Epidemiology of Colorectal Cancer Study
. We
will address three aims: (1) quantify CRC-associated T cell profiles in Latinxs from diverse genetic ancestral
backgrounds using DNA- and protein-based approaches; (2) investigate the independent associations of
genetic ancestry, epidemiologic factors, and clinical variables with T cell profiles in the tumor
microenvironment of Latinx CRCs; and (3) compare CRC-associated T cell profiles between Latinx and NHW
populations. This study is unique in leveraging the ancestral diversity of Latinos to understand the
relationships between race/ethnicity, germline genetics, tumor immunobiology, and cancer disparities.
Results will provide new avenues for understanding immunological factors contributing to disproportionate
treatment response and mortality in diverse populations of patients with CRC.

## Key facts

- **NIH application ID:** 10909148
- **Project number:** 5R01CA248931-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Stephanie L. Schmit
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $645,534
- **Award type:** 5
- **Project period:** 2021-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909148

## Citation

> US National Institutes of Health, RePORTER application 10909148, Variation in tumor-associated immune profiles and colorectal cancer outcomes (5R01CA248931-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909148. Licensed CC0.

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