# Using Single-cell and Spatial Multi-omics to Improve Adoptive Cell Therapy against Pancreatic Cancer

> **NIH NIH K99** · FRED HUTCHINSON CANCER CENTER · 2024 · $169,344

## Abstract

Project Summary/Abstract
Adoptive T cell therapy (ACT) has been effective against certain blood cancers but has had limited
success against solid tumors, such as pancreatic cancers, largely because ACT T cells become
dysfunctional within the tumor-microenvironment (TME). There is a big knowledge gap on the
causes of dysfunction in ACT T cells, mainly because there are so many T-cell-intrinsic regulators
and T-cell-extrinsic TME suppressive factors that can all potentially contribute to ACT T cell
dysfunction. With the ultimate, goal of overcoming T cell dysfunction and improving therapeutic
efficacy, I seek a more comprehensive understanding of how ACT T cells are molecularly
programmed by intrinsic epigenetic regulators to become dysfunctional, and how extrinsic TME
factors further suppress the function of ACT T cells using ACT-treated mouse models and data
from ACT-treated pancreatic cancer patients. Specifically, using single-cell multi-omics (including
epigenomics) and spatial omics, along with the computational analysis and functional experiments,
I aim to: 1) Identify targetable T cell-intrinsic epigenetic regulator(s) of ACT T cell dysfunction in
TME, 2) Identify targetable intra-TME cellular & molecular interactions that suppress ACT T cell
function. My previous wet-lab & dry-lab training, and my extensive experience with the single-cell
analysis of both cancer and the immune cells, make me well-suited for the project. The project
can significantly clarify the fundamental biology of T cell dysfunction and reveal actionable clinical
strategies for improving ACT efficacy. The proposed computational frameworks should also be
broadly applicable to a wide spectrum of contexts. The benchmark datasets should also serve as
a rich, resource to the broad field of cancer immunotherapy for hypothesis generation and testing.
My long-term goal is to lead an independent research group at a top research university, using
systems biology to study quantitative questions in immuno-oncology, especially ACT against solid
tumors. Over the course of this award, I will be supported by primary mentor, Dr. Philip Greenberg,
a pioneer of ACT therapy for cancer, with a remarkable track record in science and mentoring. My
co-mentors, Drs. Henikoff, Newell, Gottardo, Setty, Chapuis, are all renowned experts of
epigenomics, single-cell and spatial omics, computational biology and clinical science,
respectively, providing complementary training for my independence transition. They will all assist
me in navigating the transition to an independent faculty position. Work will be conducted at Fred
Hutch Cancer Center, which offers all the state-of-the art facilities required for the successful of
the Aims in addition to a collegial scientific & training environment, and strong institutional support.

## Key facts

- **NIH application ID:** 10949316
- **Project number:** 1K99CA293142-01
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Yapeng Su
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $169,344
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10949316

## Citation

> US National Institutes of Health, RePORTER application 10949316, Using Single-cell and Spatial Multi-omics to Improve Adoptive Cell Therapy against Pancreatic Cancer (1K99CA293142-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10949316. Licensed CC0.

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