Regulation of tumor-infiltrating T cells by macrophages

巨噬细胞对肿瘤浸润 T 细胞的调节

• 批准号: 10619598
• 负责人: Xiaopei Huang
• 金额: $ 43.27万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 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/10619598
• 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; Invaded; Ligands; Macrophage; 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 cell infiltration; T-Lymphocyte; Testing; Therapeutic; Tissues; Tumor Immunity; Tumor Promotion; Tumor-Derived; Tumor-associated macrophages; Up-Regulation; Work; angiogenesis; anti-PD-L1; anti-tumor immune response; antitumor effect; autocrine; cancer infiltrating T cells; exhaustion; immune checkpoint; liver cancer model; malignant breast neoplasm; novel; novel strategies; overexpression; paracrine; programmed cell death ligand 1; recruit; smoothened signaling pathway; subcutaneous; transcription factor; transcriptome; tumor; tumor growth; tumor microenvironment; tumorigenesis

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 肿瘤相关巨噬细胞（TAM）是肿瘤间质团的主要成分， 局部肿瘤影响下的表型异质性和多样的功能能力 微环境（TME）。这些TAM通常表现出抗炎的M2型表型，并且可以 通过促进血管生成、侵袭和转移以及免疫逃避来促进肿瘤生长。 然而，在很大程度上仍然不确定这些TAM如何调节体内的抗肿瘤免疫应答。 的TME。本申请的目的是了解TAM衍生的PD-L1/siglec-15在诱导细胞凋亡中的作用。 肿瘤内CD 8 T细胞功能障碍，以描述PD-L1/siglec-15上调的潜在机制， TAM以及开发新的策略来促进肿瘤内CD 8 T细胞浸润和功能， 增强抗肿瘤免疫力。该项目的长期目标是了解所需的信号， TME内TAM的功能极化及其对免疫细胞失调、癌症 发展和进展，这可能导致新的癌症治疗策略的发展。

项目成果

IL-27 Gene Therapy Induces Stat3-Mediated Expansion of CD11b+Gr1+ Myeloid Cells and Promotes Accumulation of M1 Macrophages in the Tumor Microenvironment.

IL-27 基因治疗可诱导 Stat3 介导的 CD11b Gr1 骨髓细胞扩增，并促进肿瘤微环境中 M1 巨噬细胞的积累。

• DOI: 10.4049/jimmunol.2300176
• 发表时间: 2023
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Zhu,Jianmin;Yu,Jianyu;Hu,Aiyan;Liu,Jin-Qing;Pan,Xueliang;Xin,Gang;Carson,WilliamE;Li,Zihai;Yang,Yiping;Bai,Xue-Feng
• 通讯作者: Bai,Xue-Feng