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The c-Rel Checkpoint for Immunosuppression and Immunotherapy

免疫抑制和免疫治疗的 c-Rel 检查点

基本信息

批准号：
10338110
负责人：
WARREN S PEAR
金额：
$ 50.25万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-11 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10338110
关键词：
Antineoplastic Agents Applications Grants Biochemical Blood Cancer Patient Cell Differentiation process Cell physiology Collaborations Combined Modality Therapy Complex Development Disease Drug Targeting Effector Cell Elements Family Genes Genetic Genetic Transcription Genomic approach Goals Growth Heterogeneity Human Immune checkpoint inhibitor Immunity Immunosuppression Immunotherapeutic agent Immunotherapy Individual Inflammatory Knock-out Knowledge Leukocytes Lymphoid Cell Lymphoma Malignant Neoplasms Malignant lymphoid neoplasm Mediating Mus Myelogenous Myeloid Cells Myeloid-derived suppressor cells Nature Neoplasm Metastasis Nuclear Patients Pharmacologic Substance Pharmacotherapy Play Population Research Project Grants Risk Factors Role STAT3 gene Specific qualifier value Spleen Suppressor-Effector T-Lymphocytes Testing Tumor Immunity Tumor Suppressor Proteins anti-PD1 antibodies anti-cancer antitumor effect base cancer immunotherapy cancer therapy chromatin remodeling clinical practice detector factor C genetic signature genomic locus immune checkpoint inhibitor member monocyte neoplastic cell neutrophil novel progenitor programmed cell death protein 1 programs single-cell RNA sequencing small molecule inhibitor success theories transcription factor tumor tumor growth tumorigenesis

项目摘要

The primary objectives of this research project are to characterize a new immune checkpoint and to develop a new immunotherapeutic strategy to treat cancer. Immunotherapy that targets lymphoid cell checkpoints holds great promise for curing cancer. However, a majority of cancer patients do not respond to this form of therapy. In addition to lymphoid cells, myeloid cells play essential roles in controlling immunity to cancer. Whether myeloid checkpoints exist that can be targeted to treat cancer is not well established. Myeloid-derived suppressor cells (MDSCs) are a newly identified population of leukocytes important for cancer. Depletion of MDSCs leads to markedly enhanced anti-tumor immunity in mice, and may be crucial for the success of cancer immunotherapy in humans. Despite their significance in cancer, MDSCs remain to be the least understood subset of myeloid cells. It is unclear what transcriptional program specifies MDSC differentiation; it is unknown what pharmaceutical approach can be used to target MDSCs for the treatment of cancer. This grant application is inspired by our recent discovery that the transcription factor c-Rel is required for both human and murine MDSC development and/or function, and that c-Rel inhibitors are effective for treating cancer in mice. The goals of this project are to (i) elucidate the mechanisms through which c-Rel regulates murine and human MDSCs, and (ii) establish the efficacy and the mechanisms of action of our c-Rel inhibitors for the treatment of cancer.

本研究项目的主要目的是表征一种新的免疫检查点和