# Pilot Project 2: Comprehensive characterization of somatic-environment and somatic-immune interactions in lung cancer patients with African ancestry

> **NIH NIH U54** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $52,800

## Abstract

Project Summary
Lung cancer is the leading cause of cancer death among the African American population. Although many
actionable biomarkers and targeted treatments are available to significantly prolong lung cancer survival,
patients of non-European ancestry are less likely to undergo next-generation sequencing testing than their
white counterparts. Our preliminary analysis based on real-world, observational data of clinical tumor
sequencing show that although patients with African ancestry are enriched in tobacco smoking-induced
mutational processes, there is an enrichment of TP53 and depletion of KRAS mutations, suggesting that
African ancestry may modify smoking exposure on developing KRAS-mutant lung cancer. Moreover, there is
a significant enrichment of high tumor mutation burden, which is a biomarker for immune checkpoint
inhibitors, independent of smoking status. In this project, we will identify germline ancestry or race-specific
environmental/social factors influencing the tumor genome of lung cancers. We will also assess the joint
effect of African ancestry and smoking, on somatic mutations and tumor-immune features. We will perform
immune profiling on immunotherapy -treated patients of African ancestry. We will assess the inflammatory
mediators from plasma samples of patients of African ancestry and understand how different factors in innate
response may impact patient's immunotherapy outcome. The proposed study will broaden our knowledge
about the complex relationship between genetic ancestry, environmental exposure and immune interaction
contributing to genomic differences. The findings will improve lung cancer diagnostic testing and
immunotherapy outcome prediction, and lead to future study and discovery of new treatment options for
African American patients. There is a significant racial disparity in lung cancer. In this proposal, we will
identify and characterize somatic biomarkers in tumors from patients of African ancestry. These studies will
improve clinical genomic testing and uncover therapeutic targets for this patient population.

## Key facts

- **NIH application ID:** 11012075
- **Project number:** 2U54CA137788-16
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jian Zhang
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $52,800
- **Award type:** 2
- **Project period:** 2008-09-26 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11012075

## Citation

> US National Institutes of Health, RePORTER application 11012075, Pilot Project 2: Comprehensive characterization of somatic-environment and somatic-immune interactions in lung cancer patients with African ancestry (2U54CA137788-16). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11012075. Licensed CC0.

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