# Visualizing radiation-induced tumor immune responses

> **NIH NIH R21** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $217,100

## Abstract

PROJECT SUMMARY / ABSTRACT
There is no doubt that the remarkable success of checkpoint blockade and of adoptive T cell transfer in the
clinic has positioned immunotherapy firmly as the fourth pillar of cancer treatment, next to surgery,
radiotherapy, and chemotherapy and created opportunities and challenges in equal measures. Some of the
most pressing questions we are facing include 1) relatively limited response rates, 2) the emergence of
immune-related side effects, and 3) a lack of predictive biomarkers. While combining immunotherapies, within
and across modalities will address some of these challenges, new ones are likely to arise. Certainly, radiation
therapy combined with immunotherapy can yield promising responses, but our understanding of the
mechanisms involved is very limited. Perhaps the most compelling aspect of radiation therapy lies in its
cytotoxic nature and its ability to create a hub of immunogenic tumor cell death which is characterized by a
unique biomarker signature, most notably cell surface exposure of calreticulin. Dendritic cells have the
exceptional ability to sense danger signals and relay them to the adaptive arm of the immune system by way of
licensing cytotoxic CD8 T to seek out their target and kill. The important issue is to understand when this
happens, when it doesn't happen and if it translates into systemic immunity and the ability to fight
micrometastatic disease. However, our tools to address these questions are totally inadequate. Indeed, this
proposal aims to develop powerful new tools that allow us to interrogate the tumor-host interface by
noninvasively imaging immune cells during an active immune response using engineered antibody fragments
and immunoPET. A novel calreticulin immunoPET probe will be developed, and evaluated alongside an
existing CD8 immunoPET probe for the ability to assess the induction of immunogenic cell death and the
influx and expansion of effector cells. The goal is to demonstrate that CD8 immunoPET can be used to monitor
tumor immune responses during radiation therapy; that calreticulin immunoPET can provide an early non-
invasive biomarker of immunogenic cell death and predict subsequent CD8 T cell infiltration in tumors, and that
the combination of calreticulin and CD8 imaging can be used to optimize RT dose/fractionation schedules so
as to create the optimal adjuvant to immunotherapy.

## Key facts

- **NIH application ID:** 9908059
- **Project number:** 5R21CA228542-02
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Dorthe Schaue
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $217,100
- **Award type:** 5
- **Project period:** 2019-04-05 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908059

## Citation

> US National Institutes of Health, RePORTER application 9908059, Visualizing radiation-induced tumor immune responses (5R21CA228542-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9908059. Licensed CC0.

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