# Immune Evasion in Pancreatic Cancer

> **NIH NIH K08** · UNIVERSITY OF PENNSYLVANIA · 2021 · $208,413

## Abstract

PROJECT SUMMARY
This proposal describes a five-year plan involving career development, didactic training, and basic research
focused on mechanisms of immune evasion in pancreatic cancer, which will facilitate the independent physician
scientist career of Dr. Mark Diamond in the area of cancer immunology. The candidate is interested in
understanding barriers to effective antitumor immunity against pancreatic ductal adenocarcinoma (PDAC), a
deadly cancer that is poorly T cell-infiltrated and refractory to current immunotherapy. Using tumors derived from
the ‘KPC’ murine model, Dr. Diamond has shown that PDAC cells engineered to be highly antigenic exhibit
selective immune escape in the pancreatic and peritoneal microenvironments; and that outgrowth resulted from
poor tumor-specific T cell priming by classical dendritic cells (cDCs) rather than antigen loss or tumor
immunoediting. He has additionally modeled acquired resistance following combination immunotherapy of
subcutaneous tumors, as prior studies have demonstrated the efficacy of CD40 agonist-based regimens that
promote T cell priming and can induce durable regressions. Studying late tumor recurrences following complete
responses to therapy, the candidate has shown that such tumors exhibit acquired immunotherapy resistance
and upregulation of genes in the epithelial-mesenchymal transition (EMT) pathway. Based on these data, Dr.
Diamond hypothesizes that antitumor immunity to PDAC is limited by both tumor-cell intrinsic processes
including EMT, and microenvironmental barriers within the pancreas limiting CD8+ T cell priming by cDC1s. The
candidate will address this hypothesis in the following two specific aims: (Aim 1) Define the contribution of tumor
cell plasticity mediated by EMT-inducing transcription factors on acquired resistance to immunotherapy, and
(Aim 2) Determine whether cDC1 dysfunction within the pancreatic microenvironment limits CD8+ T cell priming
against highly antigenic tumors. Dr. Diamond has assembled a team of successful physician scientists at the
University of Pennsylvania, including his primary mentor Dr. Robert Vonderheide, to serve as his advisory
committee and oversee his research and career development. Dr. Diamond will also benefit from an excellent
institutional environment that includes unique resources, mentorship, and a strong scientific community. The
comprehensive career development plan and intensive research training outlined in this proposal will allow Dr.
Diamond to acquire the necessary tools for an independent career as a physician scientist in oncology.

## Key facts

- **NIH application ID:** 10223243
- **Project number:** 5K08CA241084-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Mark Stephen Diamond
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $208,413
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223243

## Citation

> US National Institutes of Health, RePORTER application 10223243, Immune Evasion in Pancreatic Cancer (5K08CA241084-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10223243. Licensed CC0.

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