# Georgetown University Lombardi Comprehensive Cancer Center Support Grant

> **NIH NIH P30** · GEORGETOWN UNIVERSITY · 2022 · $300,625

## Abstract

This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-
CA-21-083.
 Recently, radiation therapy (RT) has been combined with immune checkpoint inhibitors (ICIs) and other
immunomodulatory agents in an effort to enhance the immune-mediated anti-tumor effects and multiple clinical
trials are ongoing to test this combination. However, while designing these trials, dose of RT, fractionation,
scheduling of the immunotherapy with respect to RT, the immunostimulatory and immunosuppressive potential
of RT that would either lead to response or resistance are not considered. Moreover, influence of status of tumor,
whether “cold” or “hot” on RT-mediated immune response and effect of RT on the immune cells in the normal
tissues are not adequately addressed. However, different RT regimens would serve as distinct
immunomodulatory ‘drugs’, generating diverse immune responses. Therefore, there is an urgent need to develop
an immune radiation response indicator (iRRi) that will consider all these factors and thereby would allow an
informed clinical trial design to maximize benefit and reduce the risk to patients, especially when
hypofractionation with high doses per fraction are used.
 Based on the above, we hypothesize that specific RT characteristics will influence the intrinsic radiation
sensitivity of various types of immune cells in normal tissues and the TME, leading to distinct immune modulatory
effects, thereby altering the immune response. To test this hypothesis, we propose the following two Specific
Aims: 1) To determine the intrinsic radiation sensitivity of different cell types of the immune compartment from
normal and tumor tissues to various radiation doses and fractionation schedules; 2) To generate an iRRi after
analysis of data in aim 1.
 RT can cause significant immunomodulation via multiple mechanisms such as by altering antigen
presentation and immunogenic cell killing. Depending on the dose and fractionation, RT can augment immune
activation or cause immune suppression. Hence, there is a need to develop an iRRi that based on the tumor
characteristics and effects on immune cells in the TME and normal tissues would help in selection of a RT
regimen that induces immune stimulatory effects. The results from this study will help in understanding the
influence of radiation characteristics on immunomodulation of the TME and normal tissues and will generate a
definitive iRRi that will be helpful in informing the design of future clinical trials on combined RT plus
immunotherapy.

## Key facts

- **NIH application ID:** 10459759
- **Project number:** 3P30CA051008-28S3
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Louis M. Weiner
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $300,625
- **Award type:** 3
- **Project period:** 2021-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459759

## Citation

> US National Institutes of Health, RePORTER application 10459759, Georgetown University Lombardi Comprehensive Cancer Center Support Grant (3P30CA051008-28S3). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10459759. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*