# Project 1

> **NIH NIH P20** · WAYNE STATE UNIVERSITY · 2021 · $314,071

## Abstract

Project Summary
The recent breakthroughs in immunotherapy, particularly immune checkpoint inhibitors (ICIs) that have received
FDA approval, have been a major advancement for lung cancer treatment. Thus far, ICI clinical trials have had
poor representation from African American patients (<4%); but in the limited data available, African Americans
show poorer response to ICIs than whites. In these therapies, antibodies that mediate the blockade of PD-1, PD-
L1, and CTLA-4 signaling are utilized to both reverse tumor-mediated immune suppression and boost anti-tumor
immune activity, however, many patients fail to benefit. ICI implementation has been guided predominantly by
disease severity, resistance to traditional treatments, and features of the tumor, but there are no universally
reliable biomarkers of response. Of the potential response biomarkers explored to date, PD-L1 expression and
tumor mutational burden (TMB) have exhibited moderate, yet incomplete capacity to predict ICI outcomes. Our
preliminary studies identified a subset of immune genes that associate with PD-L1 expression, where interferon
(IFN) signaling is a common driver, in both animal models and in tumors from NSCLC patients, where expression
of these PD-L1-associated genes differs by race. Additionally, relative to tumors from white patients, tumors from
African Americans were more likely to express components of antibody heavy and light chains, despite similar
expression of general B cell markers, which may indicate a functional difference in intratumoral B cells from
these populations. The presence of B cell-rich tertiary lymphoid structures (TLS) have recently been identified in
lung and other cancers as a potential biomarker for ICI response. Importantly, while a direct link between patient
germline genetics and response to immunotherapy remains elusive, decades of autoimmunity and inflammation
research have identified host genomic associations and racial disparities in the onset and/or severity of several
immune-mediated diseases. Our preclinical findings reveal a wide range of response rates to ICIs in genetically
diverse mice bearing genetically identical tumors, suggesting host genetic regulators may govern anti-tumor
immunity. In this study, we will build on our preliminary work to develop race-specific immune profiles associated
with IFN signaling/PD-L1 expression and presence and function of B cell-rich TLS, and we will determine whether
these profiles drive response to ICIs. Considering few African Americans were included in early ICI trials, it is
critical to conduct a comprehensive evaluation of the distinct immune profiles and their relationship to outcomes
in diverse populations. Results from these studies have the potential to guide treatment decision-making and
identify novel therapeutic targets for reduced disparities in lung cancer outcomes.

## Key facts

- **NIH application ID:** 10289603
- **Project number:** 1P20CA262735-01
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Ann G. Schwartz
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $314,071
- **Award type:** 1
- **Project period:** 2021-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289603

## Citation

> US National Institutes of Health, RePORTER application 10289603, Project 1 (1P20CA262735-01). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10289603. Licensed CC0.

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