# Elucidating genetics of response to immune checkpoint blockade in lung cancer

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $558,644

## Abstract

Abstract
 Immune checkpoint inhibitors like ipilimumab (anti-CTLA4) and nivolumab (anti-PD1) are
revolutionizing cancer treatment. Understanding the genetic basis of response and resistance to
immune checkpoint inhibitors are critical for improving outcomes with current agents and for
developing new ones. Patients can undergo dramatic remissions after treatment while others reap no
benefit. Furthermore, the immune phenotype shows substantial temperospatial variability and is
influenced by multiple variables. The rationale of this project is that there is a fundamental genetic
basis underlying response to immune checkpoint inhibitors that is poorly understood. Our preliminary
data demonstrates that response to immune checkpoint blockade is strongly determined by the tumor
mutation landscape and dictated by a specific neoantigen repertoire. We will apply a conceptually
and technically innovative, systematic, multidisciplinary, and highly collaborative approach to
elucidate the neoantigen landscape underlying response to immune checkpoint inhibitors. Our
contribution here is expected to provide unparalleled mechanistic detail on how immune checkpoint
inhibitors function and to provide biomarkers to identify patients who will benefit from PD-1 blockade.
Furthermore, building on data showing that resistance may be mediated by immune pressure and
immunoediting, we will shed light into how resistance to these drugs develop, providing definitive
evidence for causal mechanisms of anti-tumor immunity. Should our work succeed, we envision
substantial utility for similar studies for other cancers. Such an understanding will provide great insight
into the mechanisms underlying how immune checkpoint blockade works, provide much needed
precise biomarkers, and establish a foundation to develop more effective immunotherapy.

## Key facts

- **NIH application ID:** 9849754
- **Project number:** 5R01CA205426-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Timothy An-thy Chan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $558,644
- **Award type:** 5
- **Project period:** 2017-01-18 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849754

## Citation

> US National Institutes of Health, RePORTER application 9849754, Elucidating genetics of response to immune checkpoint blockade in lung cancer (5R01CA205426-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849754. Licensed CC0.

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