# NOVEL HUMORAL AND CELLULAR BIOMARKERS OF AUTOIMMUNE DISEASES CAUSED BY IMMUNOTHERAPY

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2024 · $200,107

## Abstract

Immunotherapy has transformed the treatment landscape for a wide range of human malignancies. Immune
checkpoint inhibitors (ICIs) are monoclonal antibodies that block the immune regulatory “checkpoint” receptors,
the Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4), Programmed Cell Death 1 (PD-1), or its ligand PD-
L1. ICIs produce durable responses in many patients. However, coupled with their success, these treatments
commonly evoke a wide range of immune-related adverse events (irAEs), such as diabetic ketoacidosis (DKA)
or thyroid disease, appearing to occur more frequently than originally expected. Immunotoxicity from cancer
immunotherapy occurs in up to 90%, whereas autoimmune endocrine diseases occur in approximately 50% of
patients treated with antibodies to CTLA-4 and/or PD-1/PD-L1. These irAEs can be serious or even life-
threatening, such as autoimmune type 1 diabetes (T1D) presenting in DKA, and primary adrenal insufficiency
caused by autoimmune adrenalitis. A recent study showed a marked increase of ICI-related autoimmune
diabetes; reported in over 50% of the patients, with half of these patients presenting in DKA (50.2%). Thus,
reliable biomarkers are needed to accurately stratify the risk of irAEs in patients who are candidates for these
therapies (Aim I); these biomarkers may point to novel molecular pathways that could be targeted to prevent
irAEs caused by immune checkpoint blockade (Aim II). Specifically, we will utilize the state-of-the-art single-cell
platforms to investigate and characterize the comprehensive phenotypic and functional analyses of systemic
cellular networks in patients with ICI-induced endocrinopathies. Our studies are greatly facilitated by the Baylor
College of Medicine Immunotoxicity Working Group. Understanding the immunologic factors and the biomarkers
associated with ICI-mediated inflammatory toxicities will be useful for the identification and early treatment of
ICI-induced irAEs, and it may provide new insights into the pathoetiology and treatment of autoimmune endocrine
diseases.

## Key facts

- **NIH application ID:** 10917057
- **Project number:** 5R21AI159379-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Hyun-Sung Lee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $200,107
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917057

## Citation

> US National Institutes of Health, RePORTER application 10917057, NOVEL HUMORAL AND CELLULAR BIOMARKERS OF AUTOIMMUNE DISEASES CAUSED BY IMMUNOTHERAPY (5R21AI159379-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10917057. Licensed CC0.

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