# Tissue Resident memory T cell responses to cancer

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2021 · $532,934

## Abstract

Tissue-resident memory (TRM) cells are potent mediators of immunity against infectious pathogens in
peripheral tissues. Published studies from our laboratory now establish a crucial role for TRM cells in immunity
to cancer. We show that immunotherapy-induced CD8 TRM cells mediate immunity to melanoma in the skin,
and that autoimmune vitiligo is a key host requirement for generating these durably protective TRM cells. Vitiligo
has long been recognized as a positive prognostic factor in melanoma patients. We find that the skin of vitiligo-
affected mice provides a hospitable niche for the residence of memory T cells that provide durable, protective,
antitumor immunity. We hypothesize that a diverse complement of functional memory T cells in peripheral
tissues underlies the durable tumor immunity observed in mice and melanoma patients with vitiligo and other
cutaneous inflammatory events. Our first Specific Aim will be to determine the contribution of TRM cells to
metastatic tumor protection. Mice with vitiligo also maintain protection against lung metastases, and our
preliminary data reveal a distinct population of tumor-specific TRM cells in the lungs of mice with vitiligo. We will
test the hypothesis that lung TRM cells and lymphoid TEM cells together prevent metastatic melanoma growth,
and define a core transcriptional signature for lung and skin TRM cells. Our second Specific Aim will be to define
the tumor antigen specificity of protective TRM recall responses in skin. Our data show that TRM cells in vitiligo-
affected skin have specificity for melanocyte/melanoma shared antigens, as well as a model tumor-specific
antigen. We will determine how antigen recognition affects T cell function and competition for the TRM niche,
and test the hypothesis that TRM cells with specificity for both tumor/self antigens and neoantigens mediate the
rejection of melanoma and non-melanoma tumors in the skin. Finally, our third Specific Aim will be to determine
the role of antigen-unrelated cutaneous inflammation in promoting TRM responses to melanoma. We will test
the hypothesis that melanocyte-unrelated skin inflammation can generate melanoma-specific TRM cells by
assessing TRM cell responses in skin biopsies from melanoma patients with vitiligo and other cutaneous
inflammatory events. Preclinical work will focus on a therapeutic approach for promoting TRM responses in
conjunction with immune checkpoint inhibition. Overall, this project will define the role of resident memory T
cells in the immune response to cancer. By demonstrating a fundamental role for TRM cells in host-wide
immunity to cancer, these studies are expected to have a transformative impact on the way that
immunotherapies are delivered and evaluated.

## Key facts

- **NIH application ID:** 10083716
- **Project number:** 5R01CA225028-04
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Mary Jo Turk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $532,934
- **Award type:** 5
- **Project period:** 2018-02-12 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083716

## Citation

> US National Institutes of Health, RePORTER application 10083716, Tissue Resident memory T cell responses to cancer (5R01CA225028-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10083716. Licensed CC0.

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