# Lymphoid residency of Tcf-1+ CD8+ T cells during tumor vaccine responses

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $441,601

## Abstract

Project Summary
 Tumor immunotherapies represent the most exciting advance for cancer patients in recent decades. However,
only a minor proportion of treated patients experience long-lasting benefits from current tumor immunotherapies.
A subset of tumor-specific T lymphocytes carrying features of memory or progenitor T cells has been named
“stem-like” T cells. These stem-like T cells are essential to sustain anti-tumor T cell immunity and are the major
responder to several current tumor immunotherapies. Thus, a better understanding of these stem-like T cells will
greatly facilitate the improvement of current therapies or the development of future tumor immunotherapies.
 Tissue-resident memory T cells (TRM) are a subset of non-circulating memory T cells initially discovered after
acute infections. Recently, we have discovered that stem-like T cells differentiate into tissue-resident T cells
inside tumor-draining lymph nodes, which is negatively associated with the response to tumor vaccine. In other
words, a large number of stem-like T cells lose migratory capacity and are trapped inside tumor-draining lymph
nodes.
 However, several open questions remain to be addressed regarding this newly discovered feature of stem-
like T cells. For example, what is the lineage relationship between this TRM-stem T cell subsets and other T cells
inside tumor-draining lymph nodes? Is there a connection between TRM-stem in TDLN and stem-like T cells inside
the tumor microenvironment? Whether can we manipulate TRM program of stem-like T cells to boost tumor
vaccine? In this application, we will use multiple well-established tumor models to track tumor-specific CD8+ T
cell response in the presence and absence of tumor vaccination. We will answer this series of questions focusing
on this unique T cell subset, i.e., TRM-stem. Further, our proposal will primarily focus on tumor-draining lymph
nodes, which serve as a reservoir for tumor-specific stem-like T cells. Our proposed studies will greatly advance
our understanding of stem-like T-cell biology. Importantly, we will establish a new targeting organ (tumor-draining
lymph nodes) and a novel target (the lymphoid residency program of stem-like T cells) to boost the efficacy of
tumor vaccine.

## Key facts

- **NIH application ID:** 10879481
- **Project number:** 1R01AI177345-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Nu Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,601
- **Award type:** 1
- **Project period:** 2024-02-05 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879481

## Citation

> US National Institutes of Health, RePORTER application 10879481, Lymphoid residency of Tcf-1+ CD8+ T cells during tumor vaccine responses (1R01AI177345-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10879481. Licensed CC0.

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