# Regulation of the innate immune response in the tumor microenvironment of lung adenocarcinoma

> **NIH NIH K01** · UNIVERSITY OF MINNESOTA · 2021 · $1

## Abstract

Lung cancer is responsible for more deaths in the United States than any other form of cancer. Unfortunately,
many lung cancer patients do not respond to treatments that effectively mobilize cytotoxic T cells against
tumors in other cancers (e.g. anti-PD-1/PD-L1 and anti-CTLA4). This lack of response in lung cancer is
primarily due to an inability to initiate a robust antitumor immune response. Lung cancer cells secrete the
damage-associated molecular pattern protein, High Mobility Group Box 1 (HMGB1) which has a dual function
in immunity. Although it can facilitate immune cell infiltration into tumors; its predominant function is to drive the
secretion of negative immune regulators including TGF-b and IL-10 and increase expression of programmed
death receptor ligand 1 (PD-L1). My preliminary data suggest that monounsaturated fatty acids (MUFA) are
required to prevent HMGB1 secretion from lung cancer cells. Therefore, I hypothesize that lung cancer patients
with lower concentrations of tumor-associated MUFA will have higher expression of HMGB1 resulting in an
immunosuppressive tumor microenvironment (TME). To test this hypothesis, I propose two Specific Aims: 1)
Determine the association between MUFA, extracellular HMGB1, and lung cancer in patients; 2) Evaluate the
effects of MUFA on secretion of HMGB1 and the activation of cancer-associated fibroblasts in ex vivo tumor
models. I will use lipidomic and immunological assays to determine the association between MUFA and
secreted HMGB1 in lung cancer patients. Using patient tissue explants, I will measure the effects of
pharmacologic inhibition of MUFA on secretion of HMGB1. To study the effects of genetic and pharmacologic
inhibition of MUFA on the TME, I will construct vascularized 3-dimensional bioprinted lung tumors constructed
using lung cancer cells and lung fibroblasts. This will allow characterization of immune modulating cytokines
secreted by cancer-associated fibroblasts, a dominant cell type within lung tumors. The long-term goal of this
research is to provide insight into the mechanisms by which tumors orchestrate immune suppression, and
enable the development of new strategies to overcome this immunological barrier. This K01 proposal is
designed to build upon my training background and track record in basic molecular and cancer biology, and
expand my skills as a translational researcher. My scientific advisory committee is composed of accomplished
scientists and clinicians with expertise in oncology, lung disease, lipid biochemistry, fibroblast biology and
molecular biology. The program outlined in this K01 proposal will propel me into an independent scientific
career through rigorous career development activities tailored to my specific research goals.

## Key facts

- **NIH application ID:** 10106314
- **Project number:** 1K01CA255406-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Glenn Edward Simmons
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1
- **Award type:** 1
- **Project period:** 2021-08-01 → 2021-09-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106314

## Citation

> US National Institutes of Health, RePORTER application 10106314, Regulation of the innate immune response in the tumor microenvironment of lung adenocarcinoma (1K01CA255406-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10106314. Licensed CC0.

---

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