# Immune Regulation of Disseminated Cancer Cell Dormancy

> **NIH NIH R03** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $84,709

## Abstract

SUMMARY: Most cancer patients do not die from primary tumors but from the metastatic disease. Before
formation of lethal metastases, disseminated cancer cells (DCCs) may stay dormant for up to decades, shown in
clinics as the minimal residual disease (MRD), for which effective therapies are unavailable. Immunotherapies
have made significant progress. However, most of the research focuses on primary tumors. Much less is known
for the metastatic disease, in particular for MRD. The overarching goal of this proposal is to uncover
mechanisms involved in the interaction between dormant DCCs and the immune system and therefore reveal
therapeutic opportunities for MRD before the development into a full-blown lethal disease. We will determine
the specific phenotypes of dormant DCCs and the associated immune cells relative to outgrowing metastases
using single-cell RNA-sequencing, mass cytometry (or CyTOF), and Nanostring technologies. An important
preclinical model that will be used throughout the study is the MMTV-ErbB2 mice, which develop spontaneous
dormant DCCs in secondary organs. Compared to widely used models involving transplantation of established
tumors or vaccination, this model will better mimic real-life situations in patients, as the immune system co-
evolve with the cancer cells since their inception. In Aim 1, we will determine if T cells inhibit the expansion of
DCCs via induction of dormancy and the mechanisms involved. We will test if T cell depletion allows the
reactivation of dormant DCCs in the MMTV-ErbB2 model but also an orthotopic model as a complement. We
will also test if immune cytokines induce DCC dormancy in 3D organoid cultures and in vivo and determine the
cellular source of these cytokines. In Aim 2, we will determine if DCCs use the dormancy program to induce
immune-suppression/-evasion via regulation of immune checkpoints. Specifically, we will test if dormancy-
inducing cytokines and transcription factors regulate expression of immunoregulatory factors. immune-evasion
genes to determine if the dormancy program in general is used by DCCs to avoid immune response and
therefore persist. We will also test if immune checkpoint inhibitors enable immune reactions against dormant
DCCs. Together, these approaches will allow us to understand if the immune system induces DCC dormancy, if
the dormancy program enables evasion of suppression of the immune response, and if intervention of these
processes will eliminate dormant DCCs. Thus, this study should reveal therapeutic opportunities to treat MRD
and thereby minimize the disease recurrence that kills the majority of cancer patients.

## Key facts

- **NIH application ID:** 10201082
- **Project number:** 1R03CA259656-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Julio A. Aguirre-Ghiso
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $84,709
- **Award type:** 1
- **Project period:** 2021-03-01 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201082

## Citation

> US National Institutes of Health, RePORTER application 10201082, Immune Regulation of Disseminated Cancer Cell Dormancy (1R03CA259656-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201082. Licensed CC0.

---

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