# MRI of tumor-infiltrating lymphocytes using MRI-cytometry

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $466,131

## Abstract

PROJECT SUMMARY
 This proposal seeks to further develop and validate a cell-size-based MR imaging method dubbed
MRI-cytometry as a novel approach for imaging tumor-infiltrating lymphocytes (TILs), and to evaluate its
potential as a surrogate imaging biomarker to predict treatment response to immune-checkpoint blockade (ICB)
immunotherapy. ICB is the most widespread class of immunotherapies but it poses a new challenge to assess
tumor therapeutic response. ICB induces infiltrations of TILs into tumors to kill cancer, but such increased
numbers of TILs may lead to transient tumor enlargement, which is the current indicator of tumor progression i.e.,
non-responders. Therefore, effective response to ICB could be misdiagnosed as tumor progression i.e.,
pseudo-progression. There is often a much longer waiting period than conventional treatments to verify the
persistence of tumor volume changes, which prevents timely adjustments of treatment plans particularly in
non-responder patients, causing unwanted treatment delays, costs, and risks of toxicity. Current mainstream
imaging methods require exogenous agents for labeling TILs, which significantly increases cost and risks of
toxicity. To overcome these limitations, this application proposes a novel, exogenous-agent-free approach for
imaging TILs. Because lymphocytes (5-10 μm in diameter with and without activation) are significantly smaller
than most cancer cells (10-20 µm), cell size could be used as an endogenous contrast to distinguish “small” TILs
from “large” cancer cells. The significantly increased TILs are expected to cause some unique microstructural
changes e.g., decreased mean cell sizes and increased cell fractions of “small” cells. To detect these changes,
we recently developed a cell-size-based MRI method dubbed MRI-cytometry for imaging cell size distribution
and intracellular volume fractions in vivo. Based on our preliminary data, we hypothesize that MRI-cytometry can
serve as a specific imaging biomarker of TILs, and hence can predict treatment response to ICB immunotherapy.
To test our hypothesis, we propose three specific aims: Aim 1 [development]: To further develop MRI-cytometry
imaging to overcome potentially confounding effects for accurate estimation of microstructural parameters. Aim 2
[validation]: To validate MRI-cytometry imaging to characterize lymphocyte infiltration following ICB
immunotherapy using preclinical animal models. Aim 3 [evaluation]: To evaluate MRI-cytometry to predict tumor
response to combinations of ICB immunotherapy and radiotherapy. Successful completion of this project will
establish a new exogenous-agent-free MRI tool for imaging tumor-infiltrating lymphocytes following
immune-checkpoint blockade immunotherapy. It can be used as an “add-on” to clinical MRI to reduce cost and
risks of toxicity compared with those lymphocyte labeling methods. Moreover, the proposed approach is
expected to be translated to the clinic easily, allowing clinicians to stratif...

## Key facts

- **NIH application ID:** 10419101
- **Project number:** 1R01CA269620-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Junzhong Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $466,131
- **Award type:** 1
- **Project period:** 2022-09-06 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419101

## Citation

> US National Institutes of Health, RePORTER application 10419101, MRI of tumor-infiltrating lymphocytes using MRI-cytometry (1R01CA269620-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10419101. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*