# Residual disease: unraveling immunosurveillance and immune evasion of disseminated tumor cells

> **NIH NIH U54** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $433,277

## Abstract

Project III: Latent metastasis: Immune Regulation Of Disseminated Cancer Stem Cells
PROJECT SUMMARY:
The goal of Project III is to discover mechanisms that critically regulate immune evasion by disseminated tumor
cells (DTCs) and their evolution as latent metastatic entities. We will use an integrated approach that combines
single-cell interrogation methods with unique biological models of latent metastasis from breast cancer and
lung adenocarcinoma, and novel computational strategies. Distant metastasis underlies the overwhelming
majority of cancer-related deaths and its inception is exceedingly variable. Residual DTCs may outgrow
immediately or, more frequently, linger in a viable state of replicative quiescence or mass dormancy for months
to years after infiltrating distant organs. This latency state of DTCs is accompanied with significant resistance
to anti-neoplastic therapy, which typically targets actively dividing tumor cells. Moreover, latent DTCs somehow
evade immune surveillance. The biology underlying these adaptive abilities remains poorly understood and
factors governing DTC population dynamics, whether stochastic or deterministic, remain unknown. We aim to
address this significant knowledge gap by combining massively parallel, single-cell RNA expression profiling
using a bead-based molecular barcoding technology with unsupervised learning methods to identify
stable/transitory cell states within latent, residual disease and their molecular control mechanisms. As a
complementary approach, individual cell responses to molecular perturbations will be dynamically tracked by
live cell imaging. In Aim 1 we propose to determine whether the latent state pre-exists in the primary
tumor or is induced by the stress of immunosurveillance in a host tissue. In Aim 2 we will model the
evolutionary dynamics of metastatic cells as they exit latency under growth permissive and
immunoediting conditions. Moreover, in Aim 3 we will identify key regulators of metastatic immune evasion
by probing transcriptional heterogeneity in quiescent subpopulations differentially sensitive to NK-cell mediated
elimination. The amalgamation of these approaches, combined with our deep understanding of the biology of
cancer metastasis, will promote the discovery of therapeutic strategies to eradicate or control metastasis from
its earliest stages of inception.

## Key facts

- **NIH application ID:** 9980810
- **Project number:** 5U54CA209975-05
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** JOAN MASSAGUE
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $433,277
- **Award type:** 5
- **Project period:** 2016-08-26 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980810

## Citation

> US National Institutes of Health, RePORTER application 9980810, Residual disease: unraveling immunosurveillance and immune evasion of disseminated tumor cells (5U54CA209975-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9980810. Licensed CC0.

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