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Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer

针对皮肤癌前体的免疫疗法可预防皮肤癌

基本信息

批准号：
10633109
负责人：
Shadmehr Demehri
金额：
$ 35.43万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-05 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10633109
关键词：
Actinic keratosis Address Affect Aftercare Animal Model Antigen Presentation Biological Assay CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes Calcipotriene Cells Cellular Immunity Cellular Stress Characteristics Chemopreventive Agent Clinical Clinical Trials Cytoprotection Data Development Disease remission Disseminated Malignant Neoplasm Double-Blind Method Effector Cell Epidermis Exposure to Face Fluorouracil Goals Immune Immune response Immune system Immunity Immunologic Memory Immunoprevention Immunotherapy Individual Infection Infiltration Ligands Longitudinal Studies Malignant Neoplasms Mediating Memory Morbidity - disease rate Mus Nature Outcome Outcome Study Participant Pathway interactions Patients Phase Premalignant Cell Public Health Randomized Recurrence Research Risk Risk Reduction Role Sampling Scalp structure Signal Induction Signal Transduction Site Skin Skin Cancer Skin Carcinogenesis Skin Carcinoma Squamous cell carcinoma T memory cell T-Cell Activation T-Lymphocyte TSLP gene Testing Therapeutic Uses Tissues Treatment Cost Tumor Immunity Ulcer United States Vaseline Work antitumor effect cancer diagnosis cancer immunotherapy cancer invasiveness carcinogenesis cell type clinical trial participant combat high risk immune activation innovation laser capture microdissection melanoma mortality neoplastic cell organ transplant recipient pre-clinical prevent protective effect recruit response skin cancer prevention skin squamous cell carcinoma success synergism tissue resident memory T cell transcriptome sequencing tumor

项目摘要

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.

项目总结/文摘: