Investigating the interaction between macrophages and natural killer cells in the tumour microenvironment.

研究肿瘤微环境中巨噬细胞和自然杀伤细胞之间的相互作用。

• 批准号: 2612005
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2612005
• 关键词: Investigating; interaction; between; macrophages; natural

Macrophages are innate immune cells that are abundant in the tumour microenvironment (TME) and display a range of phenotypes, including 'anti-tumour' and 'pro-tumour'. They can exert anti-tumour activities through direct killing of cancerous cells or by antibody-dependent cell-mediated cytotoxicity (ADCC). Natural killer (NK) cells are also innate immune cells and have potent anti-tumour functions including the direct lysis of target tumour cells and ADCC. Their function is governed by germline-encoded receptors, including killer cell immunoglobulin-like receptors (KIRs), one of which, known as KIR2DS2, is associated with beneficial cancer outcomes and the recognition of many solid tumours. The Khakoo laboratory has developed DNA vaccines expressing a peptide:MHC ligand for KIR2DS2 and these have been shown to enhance anti-tumour responses in vivo. It is well established that macrophages interact with NK cells in the TME and that altering their phenotypic state can boost NK cell cytotoxicity. However, there are limited studies investigating the antigen presentation abilities of macrophages towards NK cells and the DNA vaccine research has not determined the impact on other immune cells. Consequently, the aim of the PhD is to explore the activation and cytotoxicity of NK cells that are exposed to macrophages which have been manipulated to present the KIR2DS2 activating peptides. So far, a co-culture system for studying the influence of macrophages on NK cell stimulation has been established. In future experiments, this will be used to monitor changes in activation when NK cells are cultured with macrophages that have been transfected with the DNA constructs.

巨噬细胞是一种天然免疫细胞，在肿瘤微环境(TME)中含量丰富，表现出一系列的表型，包括抗肿瘤和促肿瘤。它们可以通过直接杀死癌细胞或通过抗体依赖的细胞介导的细胞毒作用(ADCC)发挥抗肿瘤活性。自然杀伤(NK)细胞也是一种先天免疫细胞，具有强大的抗肿瘤功能，包括直接裂解靶肿瘤细胞和ADCC。它们的功能受生殖线编码的受体的控制，包括杀伤细胞免疫球蛋白样受体(KIRS)，其中一种被称为KIR2DS2，与有益的癌症结局和许多实体肿瘤的识别有关。Khakoo实验室已经开发出表达KIR2DS2的多肽：MHC配体的DNA疫苗，这些疫苗已被证明可以增强体内的抗肿瘤反应。众所周知，巨噬细胞与TME中的NK细胞相互作用，改变其表型状态可以增强NK细胞的细胞毒作用。然而，关于巨噬细胞对NK细胞的抗原提呈能力的研究有限，DNA疫苗的研究还没有确定对其他免疫细胞的影响。因此，PHD的目的是探索暴露于巨噬细胞的NK细胞的激活和细胞毒性，巨噬细胞已经被操纵来呈现KIR2DS2激活肽。到目前为止，已建立了研究巨噬细胞对NK细胞刺激影响的共培养体系。在未来的实验中，这将被用来监测当NK细胞与已转染DNA构建体的巨噬细胞培养时激活的变化。