# Tissue Resident memory T cell responses to cancer

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2024 · $543,000

## Abstract

ABSTRACT
Resident memory (Trm) cells are a long-lived tissue localized CD8 T cell compartment that serves as a critical
immune barrier against cancer progression and metastasis. Our work on the prior cycle of this R01 has shown
that melanoma-specific Trm populations become distributed across skin and tumor-draining lymph nodes
(TDLNs) where they provide protection against primary and metastatic melanoma in mice. In humans, we found
that Trm populations with similar characteristics are sustained for years in the skin of melanoma survivors.
However, the field lacks a clear understanding of mechanisms governing the establishment, function, and
interconversion of Trm populations across different tissue locations. The overarching goal of this renewal
application is to define the programming requirements, trafficking requirements, and potential clinical benefit of
tumor-specific Trm cells that localize to tumor-draining lymph nodes. Based on our preliminary data that Trm
populations in lymph nodes (LNs) uniquely require type-1 interferon (IFN) signals for their generation, Specific
Aim 1 will define the mechanisms and timing of type-1 IFN production that are crucial for LN Trm formation. We
will define the critical window of type-1 IFN sensing, and the cellular interactions that govern this sensing during
Trm cell programming and maintenance. We will also determine the importance of the cGAS/STING pathway in
providing IFN signals to Trm cells in TDLNs. Thus, we expect to reveal type-1 IFN as a key cytokine for promoting
LN-restricted Trm generation. Second, based on our finding that Trm cells traffic from skin to draining LNs during
primary and recall responses to melanoma, Specific Aim 2 will define the dynamics between these tissue-
restricted compartments. By limiting T cell homing to peripheral tissue we will define a role for tissue access in
supporting Trm seeding in LNs. We will also determine the relative contribution of skin vs. tumor egress to Trm
generation in LNs. Then we will define Trm cell fate and differentiation trajectory between skin and LNs to test
the provocative hypothesis that skin serves as a reservoir for functional T cell responses against melanoma.
Finally, Specific Aim 3 will define the function and prognostic significance of LN Trm populations in patients with
melanoma and non-small cell lung cancer (NSCLC). These studies will test the hypothesis that regional LN Trm
populations correlate with resistance to metastasis to LNs. Our studies will define the function, stemness, and
plasticity of human LN Trm populations that associate with protection from metastasis. By defining mechanisms
underlying tissue-specific Trm generation, this work will support our overarching goal of generating Trm
responses throughout tissues where cancers grow and metastasize.

## Key facts

- **NIH application ID:** 10887623
- **Project number:** 5R01CA225028-07
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Mary Jo Turk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $543,000
- **Award type:** 5
- **Project period:** 2018-02-12 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887623

## Citation

> US National Institutes of Health, RePORTER application 10887623, Tissue Resident memory T cell responses to cancer (5R01CA225028-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10887623. Licensed CC0.

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