# Immunophenotype Integration for Monitoring T Cell Dynamics in Pancreatic Cancers

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $421,042

## Abstract

PROJECT SUMMARY
The overarching goal of our proposal is to accelerate the discovery of biomarkers that identify the rare group of
pancreatic ductal adenocarcinoma (PDAC) patients who respond to immunotherapy by employing a novel high-
throughput immune analysis pipeline. The majority of PDAC patients present with metastatic disease, and
treatment options are limited, yielding a dismal 5-year survival of 8%. Despite the recent remarkable progress in
immunotherapy in many cancer types, studies have failed thus far to yield substantial benefit in this
stereotypically immune-restricted disease. Our research group has long pioneered immunotherapeutic strategies
against PDAC, demonstrating that inciting immune responses against PDAC is in fact possible. Notably, we have
observed instances in which exceptional clinical responses take place. A critical challenge in discovering
biomarkers that identify these rare responders is having to undertake high-parameter characterization of the
immune responses in largely negative trials despite the lack of cost-effective high-throughput methods. Our
proposed study is uniquely suited to address this challenge for the following reasons. First, our team has
established an unparalleled resource of biospecimens from PDAC patients who have undergone a variety of
immunotherapeutic modalities including PDAC-specific vaccines, checkpoint inhibitors (anti-PD-1, anti-CTLA-4),
an epigenetic modifier (entinostat), and an IDO1 inhibitor (epacadostat). Second, our work has already led to the
discovery of key determinants of immunotherapy responses in PDAC patients: specific myeloid cell types and
germline genetics, e.g. mismatch repair defects. Third, we have recently developed high-parameter (30+ marker)
immune profiling panels for T and myeloid cell types using mass cytometry (CyTOF). Our CyTOF workflow
involves multiplexing of samples, significantly reducing the cost burden and batch-related biases during analysis.
Fourth, we have recently developed a novel computational pipeline to integrate the CyTOF-based high-
parameter T cell profiles into simplified pseudotime-based metrics that reflect the T cell states in a given sample.
This method overcomes the analytic bottleneck by obviating the need for iterative, detailed annotation of cell
types, and also by facilitating comparisons with other immunologic parameters and across disparate clinical trials.
Our progress now prompts our central hypothesis that this CyTOF-based pipeline will enhance the understanding
of T cell responses to (i) distinct immunotherapies, (ii) clinical outcomes, and (iii) other immunomodulatory factors.
Thus, using our biobank representing seven early-phase immunotherapy clinical trials in PDAC patients, we will
establish the utility of our pipeline in determining and comparing T cell dynamics specific to each immunotherapy
regimen and how they correlate with clinical outcomes. Using CyTOF-based myeloid cell profiles and an already
available germline va...

## Key facts

- **NIH application ID:** 10300626
- **Project number:** 1R21CA264004-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Won Jin Ho
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $421,042
- **Award type:** 1
- **Project period:** 2021-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10300626

## Citation

> US National Institutes of Health, RePORTER application 10300626, Immunophenotype Integration for Monitoring T Cell Dynamics in Pancreatic Cancers (1R21CA264004-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10300626. Licensed CC0.

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