# Discovering T cell proteome turnover dynamics to overcome the solid tumor microenvironment

> **NIH NIH DP5** · UNIV OF ARKANSAS FOR MED SCIS · 2023 · $374,519

## Abstract

PROJECT SUMMARY
Cellular therapies are a cornerstone in the field of cancer immunotherapy, and many consider them the next
frontier in cancer treatment. Despite the success of adoptive cell therapies for the treatment of hematologic
cancers, the question of its effective use against solid tumors remains unresolved. The extremely complex
biology of solid tumors driven by tumor heterogeneity amongst and within patients is largely the source of failure.
New approaches are needed to inform the engineering adoptive T cells and to monitor a patient’s T cell capacity
to circumvent the multitude of barriers present in solid tumors. The ability of a cell to dynamically adjust proteome
composition is essential during stress. For that reason, protein turnover rates are optimized to balance energy-
saving stability and dynamic flexibility serving as a rapid mechanism for activation or inhibition of signaling
pathways when cells respond to environmental changes. While it is common to ask the question “how do T cells
respond to stress?” we intend to shift the paradigm to asking a fundamentally different question “how are T cells
prepared for encountering stress?” The precise set of proteins T cells depend on to ensure adequate plasticity
remains elusive. We have conceived and developed a novel integrative multi-omic technique for the analysis of
proteome turnover dynamics. This technique integrates proteome, transcriptome, and protein dynamic profiling
approaches for the identification of protein “operating points”, a measure of protein dynamic nature. We
hypothesize that the ability of a T cell to adapt, through dynamic proteome control, determines persistence and
function in solid tumors. Unveiling mechanisms that endow T cells with superior adaptability and the capacity to
overcome solid tumors will be of great clinical interest in cellular therapy development. Further, identifying new
ways to determine T cell fitness in immune monitoring will not only have implications in the treatment of cancer
but, many other immune driven conditions as well. The aims of the study are 1) Define proteome turnover
changes in response to co-stimulation and exhaustion, 2) Manipulate protein turnover rates to enhance T cell
persistence, and 3) Utilize protein turnover rate measurements in patient immune monitoring.

## Key facts

- **NIH application ID:** 10690684
- **Project number:** 5DP5OD031863-03
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Brian Koss
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $374,519
- **Award type:** 5
- **Project period:** 2021-09-14 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690684

## Citation

> US National Institutes of Health, RePORTER application 10690684, Discovering T cell proteome turnover dynamics to overcome the solid tumor microenvironment (5DP5OD031863-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10690684. Licensed CC0.

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