# Cancer-Cell and T-cell Dependent Regulation of Tumor Associated Macrophages

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2020 · $198,166

## Abstract

PROJECT SUMMARY/ABSTRACT
The long-term goal of this proposal is to train the applicant to become an independent, academic physician-
scientist studying natural and therapeutic immune responses against lung cancer. The principal investigator
(PI) has previously obtained Ph.D training in immunology, as well as clinical training in internal medicine and
hematology/oncology. He is ABIM board-certified in medical oncology. This application describes a 5-year
career development program that will provide the PI a mentored educational experience with the aim of
developing new scientific expertise in molecular profiling, high-dimensional analysis, computational biology,
and mouse models of human lung adenocarcinoma. At the conclusion of the award period, the PI will have
acquired the skills necessary to achieve his ultimate goal of becoming an independent investigator in a
academic medical center studying lung cancer immunobiology and immunotherapy, and caring for patients
with thoracic malignancies. This research project will capitalize on the expertise and environment of
Washington University, which has a long-track record of developing and supporting physician-scientists. Dr.
Robert D. Schreiber will mentor the PI's scientific and career development. Dr. Schreiber's work is responsible
for the “immunoediting hypothesis” as well as the demonstration that an immunogenomics approach is able to
identify cancer neoantigens, altered proteins resulting from the genomic instability characteristic of malignancy,
and use them as a basis for effective personalized cancer vaccines. An advisory committee of scientists will
provide additional scientific and career guidance. Lung cancer is the most common cause of cancer-related
mortality worldwide. Novel immunotherapy approaches are beneficial for a subset of patients with metastatic
lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer, but responses are
often not durable. The tissue microenvironment of LUAD is characterized by lineages of tumor-associated
macrophages (TAM), which suppress T-cell responses. Our laboratory has demonstrated that TAM display a
spectrum of activation states ranging from a predominantly anti-inflammatory phenotype in progressively
growing tumors to a predominantly pro-inflammatory phenotype in tumors that respond to immunotherapy
treatment. In this proposal, we will test the hypothesis that both T-cell dependent and tumor cell-intrinsic
signals are required for TAM recruitment into the LUAD microenvironment, and that cancer neoantigens
presented by TAM determine the intratumoral function of T-cells mobilized by cancer immunotherapies. For
these studies, we will utilize a genetically engineered mouse model of human LUAD that expresses cancer
neoantigens previously identified and characterized by our laboratory. This allows us to assess immune
responses against both early stage and metastatic cancers. The identification of the precise populations of
TAM that co...

## Key facts

- **NIH application ID:** 10015239
- **Project number:** 5K08CA245215-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jeffrey P Ward
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,166
- **Award type:** 5
- **Project period:** 2019-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10015239

## Citation

> US National Institutes of Health, RePORTER application 10015239, Cancer-Cell and T-cell Dependent Regulation of Tumor Associated Macrophages (5K08CA245215-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10015239. Licensed CC0.

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