# Eco-Evolutionary dynamics of NSCLC to immunotherapy: Response and Resistance

> **NIH NIH U01** · H. LEE MOFFITT CANCER CTR & RES INST · 2020 · $603,529

## Abstract

Abstract
Worldwide, Non-Small Cell Lung Cancer (NSCLC) is the most common and among the most lethal of human
cancers with about 2 million new cases per year and a 5 year survival for metastatic disease of about 1%.
Fortunately, a number of new treatments have improved the lives of some patients with NSCLC. During the
past decade, the Moffitt Thoracic Oncology Department has pioneered new strategies using immunotherapy
for NSCLC. In almost 500 patients treated with immunotherapy at Moffitt, the response rate (CR, PR, and SD)
is 30 to 45% (2, 3). Most responses are followed by evolution of resistance and progression but some patients
in each category have experienced durable responses maintained for > 1 year (2). Our underlying hypothesis
is that the observed results from immunotherapy can be improved with sufficient understanding of the
evolutionary (cellular and molecular) and ecological (tissue) dynamics that govern response and resistance of
NSCLC to immunotherapy. We have previously demonstrated that administration of cancer therapy can be
optimized through evolutionary mathematical models that frame the complex, often non-linear underlying
dynamics. To develop such models in immunotherapy of NSCLC, we will analyze a Moffitt NSCLC
immunotherapy patient cohort all of whom were treated within an investigational protocol in which tumor
biopsies are performed prior to therapy and after 6 weeks of immunotherapy. They also underwent repeated
imaging with radiomic analyses and blood studies during the course of therapy, and many had biopsies at the
time of progression. Retrospective analysis of this cohort will investigate the evolutionary (molecular, cellular)
data as well as ecological (histological and radiological) dynamics that govern response and resistance to
immunotherapy. These investigations will be supplemented from additional ex vivo studies in which tumor and
immune cells obtained from resected primary tumors are dispersed in culture allowing the immediate response
to immunotherapy agents to be assessed. We will also perform in vitro studies that dissect the wide range of
cellular and tissue ecological engineering strategies available to NSCLC cells as well as the timescales of
immunotherapy adaptation. Finally, we will test the predictive power of our developed mathematical models to
use pre-therapy data to predict outcomes from monotherapy with PD-L1 checkpoint inhibitors. We will then
extend these models by integrating additional immunosuppressive mechanisms and test these models in a
second clinical cohort treated with combinations of PD-LI and CTLA-4 checkpoint inhibitors.

## Key facts

- **NIH application ID:** 10005265
- **Project number:** 5U01CA232382-03
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** SCOTT J. ANTONIA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $603,529
- **Award type:** 5
- **Project period:** 2018-09-19 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005265

## Citation

> US National Institutes of Health, RePORTER application 10005265, Eco-Evolutionary dynamics of NSCLC to immunotherapy: Response and Resistance (5U01CA232382-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10005265. Licensed CC0.

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