# Targeting the immunosuppressive tumor microenvironment to enhance efficacy of radiotherapy and immuno-radiotherapy for oral cancer

> **NIH NIH U01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $761,749

## Abstract

PROJECT SUMMARY AND ABSTRACT:
Radiation therapy (RT) is a mainstay of cancer treatment. However many tumors are resistant to RT, making it
possible for microscopic tumor cells to remain or travel to other parts of the body and cause cancer recurrence
at a later date. Immunotherapies can train the patient’s immune system to seek out and identify hidden tumor
cells. The combination of RT with immunotherapy is a very exciting approach, but RT can have both immune-
stimulating and immune suppressive effects, and further study is needed to understand how best to combine
RT with immunotherapy. Many scientists now believe that understanding the tumor microenvironment – the
types of cells which make up a tumor, and their interactions – is required to maximize the immune-stimulating
effects of RT. We have discovered a strategy to alter the balance of cells in the tumor microenvironment of oral
cancer and other solid tumor types, by simultaneously targeting immunosuppressive myeloid derived
suppressor cells (MDSC) and regulatory T cells (Treg), so that immune-stimulating effects of RT predominate.
Studies in mouse tumors show that this strategy is particularly effective when combined with an
immunotherapy approach called “checkpoint inhibition” that targets molecules that limit effectiveness of anti-
tumor T cells. This leads to our scientific hypothesis that tumor-infiltrating MDSC and Treg render the tumor
microenvironment resistant to immune activation by RT and/or checkpoint inhibition, and limit the induction of
tumor-specific CD8+ T cells and other immune effector immune cells. The goals of this proposal are to 1)
determine whether modulating the tumor immune microenvironment enhances responsiveness of oral cancer
to RT and/or checkpoint inhibition, leading to long-lasting and powerful anti-tumor effects; 2) determine the
immunological mechanisms which make these combination therapies effective; and 3) develop a novel drug
formulation which will make this approach more effective and suitable for testing in clinical trials. We will
accomplish these goals by carrying out the following specific aims:
In Aim 1 we will functionally dissect the immune mechanisms by which MDSC contribute to radioresistance
in mouse oral cancer models.
In Aim 2 we will assess the ability of dual targeting of MDSC and Treg to sensitize oral cancer to treatment
with RT + anti-PD-1 and induce durable protective memory responses.
In Aim 3 we will develop a novel drug delivery system that can enhance delivery of inhibitors of MDSC function
directly to the tumor and tumor-infiltrating MDSC.

## Key facts

- **NIH application ID:** 10291087
- **Project number:** 7U01DE028233-04
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Ananth V Annapragada
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $761,749
- **Award type:** 7
- **Project period:** 2020-09-02 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291087

## Citation

> US National Institutes of Health, RePORTER application 10291087, Targeting the immunosuppressive tumor microenvironment to enhance efficacy of radiotherapy and immuno-radiotherapy for oral cancer (7U01DE028233-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10291087. Licensed CC0.

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