# Optimizing anti-tumor immunity for maximal therapeutic efficacy in Colorectal Cancer

> **NIH VA IK2** · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · 2024 · —

## Abstract

Project Summary:
Colorectal cancer (CRC) accounts for nearly 10% of all cancer diagnoses in the VA system1.
Additionally, the VA system treats 3% of the total number of US cases of CRC and 6% of all US
cases in males2. The immune response to CRC is critical to therapeutic response and survival.
Cytotoxic T cells (CTL) are the end mediators of the anti-tumor response. As expected, tumor
associated CTL are also associated with treatment response and survival in CRC. In our murine
model of colorectal cancer, we have found that depending on the therapeutic regimen used, there
is a differential effect on the number and type of CTL in the tumor microenvironment. FOLFOX
chemotherapy, the first-line chemotherapeutic regimen in CRC, controls tumor growth better than
individual arms alone and engenders increased antigen specific CTL in the tumor
microenvironment. Our understanding of how FOLFOX chemotherapy affects tumor associated
CTL type and response is unknown. This information is critical for the future design of clinical
trials testing novel therapeutic combinations in CRC. In this VA CDA-2 proposal, we will study the
differential effect of FOLFOX chemotherapy on CTL type, function, signaling, exhaustion, and
memory. Additionally, we will test the effect of innate immune sensing to induce CTL and work in
combination with FOLFOX in CRC.
A multi-disciplinary team of VA Merit and NIH-R01 funded clinician-scientists and basic
scientists have been recruited to comprise a mentorship team designed to ensure the success
of the application candidate. The data and skill development outlined in this proposal will ensure
the development of a successful research career for the candidate and pre-clinical data in
support of future clinical trials in CRC utilizing immune based therapy in combination
chemotherapy.

## Key facts

- **NIH application ID:** 11032296
- **Project number:** 7IK2BX004346-06
- **Recipient organization:** LOUIS STOKES CLEVELAND VA MEDICAL CENTER
- **Principal Investigator:** Jonathan B. Mitchem
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 7
- **Project period:** 2018-10-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11032296

## Citation

> US National Institutes of Health, RePORTER application 11032296, Optimizing anti-tumor immunity for maximal therapeutic efficacy in Colorectal Cancer (7IK2BX004346-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11032296. Licensed CC0.

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