Regulation of tumor-infiltrating T cells by macrophages

项目摘要 肿瘤相关巨噬细胞(TAMs)是肿瘤间质的主要成分，表现出很大的 局部肿瘤影响下的表型异质性和功能多样性 微环境(TME)。这些TAM通常表现出抗炎的M2型表型，并可以 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，这些TAM如何在体内调节抗肿瘤免疫反应在很大程度上仍未明确。 TME。本应用的目的是了解衍生的PD-L1/Siglec-15在诱导 肿瘤内CD8 T细胞功能障碍，以阐明PD-L1/siglec-15上调的机制 TAMS以及开发新的策略来促进CD8 T细胞在肿瘤内的渗透和功能 增强抗肿瘤免疫力。该项目的长期目标是了解 TME内TAMs的功能极化及其在免疫细胞失调、癌症中的作用 发展和进展，这可能导致新的癌症治疗策略的发展。

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.