# Quantitative and Spatially-Resolved Analysis of the Tumor Immune Contexture for Optimal Diagnosis and Treatment of Lung Cancer

> **NIH NIH R37** · YALE UNIVERSITY · 2023 · $375,309

## Abstract

Summary:
PD-1 axis blockers induce durable clinical responses in ~20% of patients with non-small cell lung cancer
(NSCLC). However, most patients do not benefit from treatment and those who initially respond ultimately
develop acquired resistance. There are limited treatment options for these clinical scenarios. To substantially
reduce NSCLC mortality, it is imperative to: i) Identify novel biomarkers for optimal selection of patients for
treatment; ii) Uncover immunotherapy targets beyond the PD-1/PD-L1 axis that may serve to treat patients with
refractory tumors; and iii) Reveal the role of immunity during tumor progression to design early therapeutic
interventions. Recent studies from our group identified baseline T-cell dysfunction and LAG-3 upregulation as
key determinants for resistance to PD-1 blockade in NSCLC. We have also found that LAG-3 signaling induces
T-cell apoptosis and identified FGL1 as major inhibitory LAG-3 ligand in cancer. We hypothesize that
engagement of the LAG-3/FGL1 pathway mediates dominant immune evasion and T-cell dysfunction/death in a
subset of NSCLCs insensitive to PD-1 therapies. In this project and through 3 complementary aims, we will
leverage our expertise in cancer immunobiology and biomarkers to: i) Determine the biomarker value of
measuring functional TIL profiles in human NSCLC; ii) Analyze the mechanisms and role of LAG-3/FGL1
interaction as immunomodulatory target in human lung malignancies; and iii) Examine the role LAG-3/FGL1
pathway and immune contexture in carcinogenesis and early lung cancer progression. The results from this work
will accelerate translation of research concepts into the clinic for establishment of novel biomarkers, support
interpretation of clinical trials and design optimal treatment modalities for early-stage and advanced lung cancer.

## Key facts

- **NIH application ID:** 10683079
- **Project number:** 5R37CA245154-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Kurt A Schalper
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $375,309
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683079

## Citation

> US National Institutes of Health, RePORTER application 10683079, Quantitative and Spatially-Resolved Analysis of the Tumor Immune Contexture for Optimal Diagnosis and Treatment of Lung Cancer (5R37CA245154-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10683079. Licensed CC0.

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