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Regulation of tumor-infiltrating T cells by macrophages

巨噬细胞对肿瘤浸润 T 细胞的调节

基本信息

批准号：
10297968
负责人：
Xiaopei Huang
金额：
$ 44.12万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10297968
关键词：
Anti-Inflammatory Agents CD8-Positive T-Lymphocytes CXCL10 gene CXCL9 gene Cell Differentiation process Cell Proliferation Cells Chimera organism Data Development Engineering Erinaceidae Functional disorder Heterogeneity Human Immune Immune Evasion Lead Ligands Malignant Neoplasms Malignant neoplasm of brain Malignant neoplasm of gastrointestinal tract Malignant neoplasm of lung Malignant neoplasm of prostate Mediating Modeling Mus Myeloid Cells Neoplasm Metastasis PD-1 blockade Pathway interactions Phenotype Play Primary carcinoma of the liver cells Production Regulation Role SHH gene Signal Transduction Skin Cancer Solid Neoplasm Stromal Cells Stromal Neoplasm T-Lymphocyte Testing Therapeutic Tissues Tumor Immunity Tumor-Derived Tumor-associated macrophages Tumor-infiltrating immune cells Up-Regulation Work angiogenesis anti-PD-L1 anti-tumor immune response antitumor effect autocrine exhaustion immune checkpoint macrophage malignant breast neoplasm novel novel strategies overexpression paracrine programmed cell death ligand 1 recruit sialic acid binding Ig-like lectin smoothened signaling pathway subcutaneous transcription factor transcriptome tumor tumor growth tumor microenvironment tumorigenesis

项目摘要

Project Abstract Tumor-associated macrophages (TAMs), a major component of the tumor stromal mass, demonstrate great phenotypic heterogeneity and diverse functional capabilities under the influence of local tumor microenvironment (TME). These TAMs generally display an anti-inflammatory, M2-type phenotype and can facilitate tumor growth by promoting angiogenesis, invasion and metastasis, as well as immune evasion. However, it remains largely undefined exactly how these TAMs regulate anti-tumor immune responses within the TME. The objective of this application is to understand the role of TAM-derived PD-L1/siglec-15 in inducing intratumoral CD8 T cell dysfunction, to delineate mechanisms underlying PD-L1/siglec-15 upregulation in TAMs as well as to develop novel strategies to promote intratumoral CD8 T cell infiltration and function in favor of enhancing anti-tumor immunity. The long-term objective of this project is to understand signals required for functional polarization of TAMs within the TME, and its contributions to immune cell dysregulations, cancer development and progression, which may lead to the development of novel cancer therapeutic strategies.

项目摘要