# P53-dependent immunogenic DCs in the tumor microenvironment

> **NIH NIH R50** · AUGUSTA UNIVERSITY · 2020 · $205,858

## Abstract

The field of tumor immunotherapy is progressing rapidly. New pathways and molecular targets are being
identified for translation and treatment, and more are urgently needed. With this growing level of insight comes
the pressing need for molecularly-defined, scientifically rigorous in vivo preclinical models, in which to discover
new mechanisms, and test the new hypotheses. Even though our current “single-agent” approach can be
dramatic in some patients, most of the patients, with most kinds of tumors, do not yet receive any benefit from
immunotherapy. Thus, to move the field forward to the next level of clinical efficacy, the emphasis will be on
discovering new targets; identifying synergistic combinations; and finding ways to integrate innovative
immunotherapy with standard-of-care chemotherapy and radiation. The PI, Dr. Madhav Sharma, is a senior
and highly productive Principle Research Scientist (non-tenure track), who has been associated for 17 years
with the laboratory of the Unit Director, Dr. David Munn. As a research specialist in this group, Dr. Sharma
has developed sophisticated preclinical models in tumor immunology, and used these for high-impact,
innovative new basic-science discoveries, with high translational potential. The current proposal focuses on a
novel population of potently immunogenic dendritic cells (DCs), arising in tumors during immunotherapy.
These share attributes of “conventional” CD103+ cDCs, but they differentiate directly from monocytic MDSCs,
already pre-positioned in the tumor, in response to inflammation. The scientific premise of the proposal is
that this specialized population of myeloid-lineage Ly6c+CD103+ DCs is a critical driver of anti-tumor immune
responses during multiple forms of immunotherapy, in both mice and humans; and that it is possible to
therapeutically amplify the number of these cells in the tumor, so as to markedly enhance the effectiveness of
immunotherapy. The translational importance of these findings is that they identify the transcription factor
p53 in host myeloid-lineage cells as the key driver of this Ly6c+CD103+ DC population; thus revealing
myeloid-lineage p53 as a previously unsuspected target for immunotherapy. Myeloid p53 can be efficiently
targeted by re-purposing existing p53-agonist (MDM2-inhibitor) drugs already under clinical development for
other indications. All of these innovative preclinical discoveries have resulted directly from Dr. Sharma’s
sustained and highly productive program of preclinical research in Dr. Munn’s group.

## Key facts

- **NIH application ID:** 9999534
- **Project number:** 5R50CA232983-03
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Madhav Datt Sharma
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $205,858
- **Award type:** 5
- **Project period:** 2018-09-05 → 2021-03-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999534

## Citation

> US National Institutes of Health, RePORTER application 9999534, P53-dependent immunogenic DCs in the tumor microenvironment (5R50CA232983-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999534. Licensed CC0.

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