# Admin. Suppl. for NCI CCSG/Moonshot Grant to Develop Immune Radiation Response Index (iRRI) for Immune Cells from Normal and Tumor Microenvironments

> **NIH NIH P30** · OHIO STATE UNIVERSITY · 2022 · $167,344

## Abstract

SUMMARY
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-
21-083. The interplay between radiation therapy (RT) in cancer treatment and the host immune system is
complex. RT can have local therapeutic effects through direct damage to cancer cells, or can stimulate a
systemic anti-tumor immune response. The benefits of combining RT and immunotherapy have been reported
in several pre-clinical models and case reports. However, despite the sustained and deep responses observed
in some patients, many cancer patients do not respond to these agents emphasizing the need for further
improvements in treatment strategies. Interestingly, the effects of radiation on the TME vary with dose and
fractionation schedules. In addition to its role in immune activation, RT can also cause chronic inflammation,
release of cytokines, and increased infiltration of immunosuppressive cells in the TME potentially rendering
decreased tumor responses in a paradoxical manner. However, knowledge is lacking on the immunologic impact
of different RT regimens, especially in comparison with changes to RT in human tumor tissues.
This proposal aims to investigate the effects of different doses and fractionation of RT on innate and adaptive
immune cells using both pre-clinical syngeneic murine melanoma and non-small cell lung cancer (NSCLC) flank
models. We will correlate and compare these changes to those within formalin-fixed paraffin-embedded (FFPE)
tissue surgical samples from human patients with brain metastases from melanoma and NSCLC recently treated
with RT or non-irradiated patient samples. Comparing with non-irradiated control samples, we will determine the
effects of RT on tumor immunogenicity (PD-L1, MHC Class I levels) and on immune cell absolute numbers in
the tumor microenvironment (TME). Using a multispectral imaging technique, we will measure RT induced CD4+
T cell, CD8+ effector T cells, regulatory T cells, myeloid derived suppressor cells (MDSCs), tumor associated
macrophages (TAMs), and dendritic cell influx into the TME and secondary lymphoid tissues in animal models.
Serum cytokine levels following RT will also be measured using cytokine array multiplex panels. Similarly, a
multispectral imaging technique will measure RT induced changes to immune cell populations in human tumor
surgical specimens. Since RT can induce changes in the gene and protein expression profiles of both tumor and
immune cells, and transcriptomic landscapes can be associated therapeutic outcomes, the cell-type specific
transcriptional profile in the TME of FFPE human tumor samples will be determined using single cell
transcriptomic assays. Our multi-disciplinary team plans to systematically categorize the effects of different RT
regimens on immune cells and define a radiation response index (i-RRI) on a dose scale (in Gy). We aim to
define immune cells as being either “radiation sensitive” or “radiation resistant” at particular dose...

## Key facts

- **NIH application ID:** 10459993
- **Project number:** 3P30CA016058-46S2
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Zihai Li
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $167,344
- **Award type:** 3
- **Project period:** 1997-09-12 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459993

## Citation

> US National Institutes of Health, RePORTER application 10459993, Admin. Suppl. for NCI CCSG/Moonshot Grant to Develop Immune Radiation Response Index (iRRI) for Immune Cells from Normal and Tumor Microenvironments (3P30CA016058-46S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10459993. Licensed CC0.

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