# Identification of circulating and tissue-specific autoimmune responses in checkpoint inhibitor-induced immune-related adverse events

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $199,098

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this resubmission application is to train David Y. Oh, MD PhD, a medical oncologist and
immunologist, providing him with the skills to become an independently funded laboratory investigator studying
immune-related adverse events (IRAEs) after checkpoint inhibitors (CPIs). CPIs are cancer immunotherapies
that activate anti-tumor immune responses leading to improved survival in several cancers, but also trigger
IRAEs which are autoimmune responses against normal tissues that represent an increasing source of morbidity
for cancer patients. The proposed training plan incorporates didactic and practical experience to provide a
foundation in the following areas which complement his existing expertise and are critical to accomplishing his
research goals: (1) fundamental B cell biology including B cell-driven autoimmunity and methods for autoantibody
discovery and validation, (2) next-generation sequencing methods and analysis including single-cell approaches
appropriate for human patient samples, (3) methods in clinical trial design including biostatistics and correlative
science. The research plan addresses key limitations in our understanding of IRAE mechanisms by studying
both cellular (T cell) as well as humoral (B cell) responses to autoantigens during IRAEs. By studying IRAE
tissues, the proposed research will identify and validate the specific immune responses that may be directed
towards tissue-specific autoantigens. Dr. Oh’s hypothesis is that autoimmune responses in IRAE-affected tissues
are newly induced by CPIs and not present before treatment, and the tissue autoantigens responsible for IRAEs
are targeted by a distinct subset of tissue-resident T cells and by specific autoantibodies. The Aims of the
proposed research are: (1) to dissect the antigenic and functional profile of autoreactive T cells that are enriched
in IRAE-affected tissues, and (2) to discover and validate autoantibody responses to tissue-specific autoantigens
that are associated with IRAEs. The training and research plan encompass a structured combination of formal
coursework, tutorials, mentorship, and hands-on research experience within the dynamic environment of the
University of California, San Francisco, a renowned center for basic and translational research. Dr. Oh’s training
will be conducted under the mentorship of Dr. Lawrence Fong, a leading translational researcher in cancer
immunotherapies who co-directs the Parker Institute for Cancer Immunotherapy at UCSF, and a distinguished
advisory committee of physician-scientists with extensive mentorship experience and expertise in each area
corresponding to Dr. Oh’s training and research aims. The intermediate goal of this proposal is to identify IRAE-
specific immune responses that will be the basis for an R01. The long-term goal of this award is to provide the
skills to enable Dr. Oh to become a leader in mechanistic studies of IRAE samples from immunotherapy-treated
patients using...

## Key facts

- **NIH application ID:** 9881237
- **Project number:** 5K08AI139375-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** David Yoonsuk Oh
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,098
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881237

## Citation

> US National Institutes of Health, RePORTER application 9881237, Identification of circulating and tissue-specific autoimmune responses in checkpoint inhibitor-induced immune-related adverse events (5K08AI139375-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9881237. Licensed CC0.

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