# Immunogenomic determinants of response and resistance to neoadjuvant anti-PD-1 in resectable NSCLC

> **NIH NIH R37** · JOHNS HOPKINS UNIVERSITY · 2021 · $374,578

## Abstract

Summary
More than 1.8 million people worldwide are diagnosed with non-small cell lung cancer (NSCLC) every year.
Of these patients, 20% present with stage I or II disease. For these patients, surgical resection remains the
first course of treatment, however even in apparently curative surgery 50% of stage I and 70% of stage II
NSCLC patients will recur and eventually die of the disease. Neoadjuvant and adjuvant chemotherapy are
standard treatments for resectable NSCLC and are used with the dual goals of reducing tumor size prior to
surgery and preventing relapse. We recently completed a clinical trial of neoadjuvant PD-1 blockade in
resectable NSCLC and demonstrated an impressive 45% major pathologic response rate. To date, however,
the mechanisms underlying response to this treatment are unknown. In the study proposed here, we will
leverage this existing clinical trial and the biospecimens already obtained to elucidate the functional impact of
PD-1 blockade on tumor-reactive T cells and to determine how differential T cell transcriptional programs
facilitate pathologic response. We will implement a novel approach, using the T cell receptor as a molecular
barcode for antigen-specificity using basic and single cell sequencing technologies, to understand the
dynamic interplay of different T cell subsets and how their transcriptional programming is modified by anti-
PD-1. Identification of targetable markers of response or resistance, development of novel bioinformatic
approaches to analyze neoantigen-specific single cell data, and enumeration of immunogenomic
determinants of pathologic response to neoadjuvant PD-1 blockade are only some of the key outcomes of
this study.

## Key facts

- **NIH application ID:** 10209167
- **Project number:** 1R37CA251447-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Kellie Nicole Smith
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $374,578
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209167

## Citation

> US National Institutes of Health, RePORTER application 10209167, Immunogenomic determinants of response and resistance to neoadjuvant anti-PD-1 in resectable NSCLC (1R37CA251447-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10209167. Licensed CC0.

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