# High dose radiation therapy to direct immune responses to pancreatic cancer

> **NIH NIH R01** · PROVIDENCE PORTLAND MEDICAL CENTER · 2020 · $391,875

## Abstract

PROJECT SUMMARY
The critical preliminary data for this proposal is that in preclinical models, pre-existing tumor-resident T cells
are both necessary and sufficient for tumor control by radiation therapy and immunotherapy. We demonstrate
that in poorly immunogenic tumors, cross-presenting dendritic cells in the tumor-draining lymph node may be
playing no significant role in tumor control. In these models, radiation and immunotherapy are an effective
means of local control but fail to engender new systemic immunity. The aim of this proposal is to understand
how radiation interacts with tumor resident T cells for local control, and how to restore cross-presentation of
tumor-associated antigens to generate new systemic anti-tumor immune responses. We hypothesize that the
endogenous vaccine effect of radiation therapy is limited in poorly immunogenic tumors, and current success
relies on amplifying pre-existing anti-tumor immunity. The specific aims of this study are to 1: Test the
hypothesis that in the presence of pre-existing immunity, tumor control by radiation therapy and
immunotherapy occurs independent of cross-presentation and new immune responses; 2: Test the hypothesis
that deficient DC cross-presentation limits the ability of radiation therapy to initiate new systemic anti-tumor
immune responses; 3: Test the hypothesis that regulation of antigen presentation and cross-presenting DC
can be assessed in patient tumors using genetic analysis. Our study design incorporates CT-guided radiation
therapy and results are validated in multiple tumor models including those from genetically engineered
spontaneous models, using a range of RT doses and fractionations. Our analyses of clinical samples use high
quality bioinformatic approaches that allow us to evaluate the infiltrating immune cells and antigen presentation
in patient tumors. These are applied to a unique clinical study that allows us to validate our preclinical
observations in patients.

## Key facts

- **NIH application ID:** 9957023
- **Project number:** 5R01CA182311-07
- **Recipient organization:** PROVIDENCE PORTLAND MEDICAL CENTER
- **Principal Investigator:** Michael James Gough
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,875
- **Award type:** 5
- **Project period:** 2014-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957023

## Citation

> US National Institutes of Health, RePORTER application 9957023, High dose radiation therapy to direct immune responses to pancreatic cancer (5R01CA182311-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9957023. Licensed CC0.

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