# Project 1: Delta immune Ecology of NSCLC

> **NIH NIH U54** · H. LEE MOFFITT CANCER CTR & RES INST · 2024 · $475,697

## Abstract

Summary – Project 1
Project 1 will study the ∆-Ecology of tumor-immune interactions in NSCLC, with a focus on KRAS-mutant
cancers. Immunotherapy has demonstrated response rates of 30 to 45%. Most responses are followed by
evolution of resistance and progression. Recently we have quantified the immune ecology of these cancers
from pre-treatment biopsies and found unique ecological interactions that predetermine therapy response. A
focus of this proposal will be to use both pre- and on-treatment biopsies from a clinical trial to quantify the
immune ∆-Ecology during therapy. We will use a computational multiplexed-image analysis pipeline that takes
whole-slide images and segments the data into cells and quadrats to analyze the spatial and spatiotemporal
features representing ecological changes that drive tumor progression. We will then harness this analysis as a
spatiotemporal biomarker to alter treatment strategies via mathematical modeling. The computational
infrastructure will be grounded in mechanistic models, spatial statistics, machine learning, and deep learning.
Targeted therapies are also a key component in the treatment of this disease. In an exciting discovery,
inhibitors that target KRAS-G12C mutant cancers have been developed and have demonstrated clinical
efficacy. Furthermore, preclinical work has demonstrated that these inhibitors alter the immune ecology of
tumors, offering promise that combination targeted therapy and immunotherapy can significantly improve
responses. We will perform in vivo work with murine tumors and deep ecological analysis of human tumors to
determine the mechanisms of immune ∆-Ecology fomented by KRAS inhibitors, and probe combination
therapies that synergize the anti-tumor response. Our ultimate goal is the development of a predictive model of
∆-Ecology that delivers novel treatment strategies and improves outcomes, for use in future clinical trials.

## Key facts

- **NIH application ID:** 10930171
- **Project number:** 5U54CA274507-02
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Alexander Robertson Allan Anderson
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $475,697
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930171

## Citation

> US National Institutes of Health, RePORTER application 10930171, Project 1: Delta immune Ecology of NSCLC (5U54CA274507-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10930171. Licensed CC0.

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