# Optical control of T cell metabolism

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2021 · $179,988

## Abstract

PROJECT SUMMARY
Adoptive cell transfer introduces engineered tumor-targeting cytotoxic T lymphocytes (CTLs) to patients. While
this immunotherapy is effective against hematologic malignancies, it is ineffective against solid tumors due in
part to the immunosuppressive microenvironment. The tumor microenvironment presents many challenges to
CTL energy production including oxygen and glucose depleted environment and tumor expression of inhibitory
ligands that limit nutrient uptake by T cells. These conditions render CTLs hypo-responsive. Naïve T cells rely
on OxPhos for energy. Following activation, the highly proliferative effector T cell undergoes metabolic
remodeling and shifts reliance from OxPhos to glycolysis. As such, T cells are considered metabolically plastic
and massive metabolic alterations are a normal part of T cell development. However, how metabolic alterations
impact cell fate and function at their target tissue sites remain unknown. This leads us to our central hypothesis
that boosting metabolism at the tumor site can prevent CTL dysfunction and improve adoptive cell transfer
immunotherapy outcomes. Unfortunately, to date there has been no means of testing this hypothesis directly.
Metabolic reprogramming is commonly studied through the global administration of drugs that lack target
selectivity. We aim to circumvent this limitation through our novel optogenetic systems that allow us to directly
modulate T cell metabolism. We will; (1) investigate the impact of the mitochondrial membrane potential on CD8+
T cell effector functions, (2) regulate local cytokine signals to control T cell metabolic programs in the tumor
microenvironment, and (3) develop deep tissue immunomodulation approaches. The completion of the proposed
study will enable us to gain a comprehensive analysis of immunity that can provide new insight into how T cells
interact with the tumor microenvironment.

## Key facts

- **NIH application ID:** 10070598
- **Project number:** 5R21CA242843-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Minsoo Kim
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $179,988
- **Award type:** 5
- **Project period:** 2019-12-13 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070598

## Citation

> US National Institutes of Health, RePORTER application 10070598, Optical control of T cell metabolism (5R21CA242843-02). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10070598. Licensed CC0.

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