# The tumor ecosystem in cancer progression and immunotherapeutic response

> **NIH NIH U54** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $638,655

## Abstract

Project II. The tumor ecosystem in cancer progression and immunotherapeutic response
PROJECT SUMMARY
The goal of this project is to identify the ecological interactions between cancer and immune cells that govern
cancer dynamics and response to therapy. We start from the idea that a tumor can be considered an
ecosystem or organ, where multiple accessory cell types are interconnected and communicate with each other
and with tumor cells, which serve as their clients. Through systems analysis and modeling of functional
interactions in the tumor ecosystem on different scales including cellular, protein, and gene expression
dynamics at a population and single cell levels this proposal will seek to identify key cellular and molecular
regulatory elements in the tumor microenvironment and potential means of their manipulation for therapeutic
benefit. We will explore features of, and relationships between, multiple accessory cell types and tumor cells, in
experimental models of skin and lung cancer in mice and in human cancer patients (Aim 1). The accessory
cells include myeloid cells, dendritic cells, innate lymphoid cells (ILC), neutrophils, eosinophils, endothelial
cells, fibroblasts, and regulatory T (Treg) cells. We will also investigate features of mediators of anti-tumor
immunity including NK cells, CD4 and CD8 T cells and their specialized subsets. We will use perturbation of
the tumor ecology impacting its progression in mice and human patients by established and novel
immunotherapeutic modalities including PD1 and CTLA4 blockade and Treg cell depletion. The impact of
these perturbations will be assessed through comprehensive analysis of cellular dynamics and states in
relation to biological and clinical outcomes to generate predictive models from the data (Aim 2). We will then
validate key interaction components in the tumor ecosystem by modeling cell-cell interactions in vitro using
tissue mimetic systems and in silico using agent-based models (Aim 3).
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## Key facts

- **NIH application ID:** 9980809
- **Project number:** 5U54CA209975-05
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Alexander Y Rudensky
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $638,655
- **Award type:** 5
- **Project period:** 2016-08-26 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980809

## Citation

> US National Institutes of Health, RePORTER application 9980809, The tumor ecosystem in cancer progression and immunotherapeutic response (5U54CA209975-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980809. Licensed CC0.

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