# Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $342,498

## Abstract

Project Summary/Abstract:
Recent success in utilizing patients’ own immune cells to combat metastatic cancers highlights the ability of the
immune system in providing sustained remission for patients with late-stage cancers like melanoma. However,
the role of the immune system in eliminating premalignant cells and preventing their progression to invasive
cancers remains uncertain. To determine the benefit of activating the immune system to prevent cancer
development and recurrence, we study the immune pathways that lead to effective immune activation against
early phases of skin cancer development. Non-melanoma Skin cancers (NMSCs) are collectively the most
commonly diagnosed cancers in the United States. cutaneous squamous cell carcinoma (SCC) is associated
with severe morbidities including disfigurement, ulceration and infection, and a mortality rate similar to that of
melanoma. Importantly, the SCC precursors can be clinically identified and treated. Based on compelling
preclinical data, we have performed a randomized double-blind clinical trial in which we find topical calcipotriol
together with 5-fluorouracil (5-FU) to promote a robust adaptive immune activation against skin cancer
precursors, actinic keratoses, and their complete clearance. Importantly, this immunotherapy led to a
significantly lower risk of SCC compared to 5-FU monotherapy group in 3 years post-trial. In order to determine
the precise mechanism of calcipotriol plus 5-FU action against early premalignant cells in the skin, and to fully
harness its potential to prevent skin cancer, we aim to (1) determine the signals that direct the immune cells to
the premalignant cells treated with calcipotriol plus 5-FU combination, (2) investigate the mechanism by which
these activated immune cells eliminate the targeted tumor cells, and (3) identify the immune cells and factors
that mediate the long-term protective effects of calcipotriol plus 5-FU against SCC. The outcomes of the
proposed research will establish a fundamental role for immune activation in combating the early stages of skin
cancer development and provide the rationale for the use of calcipotriol plus 5-FU combination in skin cancer
immunotherapy and immunoprevention.

## Key facts

- **NIH application ID:** 10228570
- **Project number:** 5R01AR076013-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Shadmehr Demehri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $342,498
- **Award type:** 5
- **Project period:** 2019-07-05 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228570

## Citation

> US National Institutes of Health, RePORTER application 10228570, Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer (5R01AR076013-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10228570. Licensed CC0.

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