Introduction

The purpose of this study was to examine the effects of elevated Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) on the immune response in the tumor microenvironment.

Methodology

HPRT expression was evaluated in cancer patients and correlated with cytokine expression, survival, and immune cell infiltration. An HPRT knockdown cell line was created to evaluate HPRT impact on purine expression and subsequent purine treatment was administered to immune cells to determine their influence on cell activation.

Results

HPRT expression was negatively correlated with the general expression of both pro-inflammatory and anti-inflammatory cytokines. Additionally, HPRT expression was also negatively correlated with the infiltration of immune cell subsets: B-cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells (p < 0.001) and CD8 + T-cells (p < 0.01). When HPRT was knocked down in a Raji cell line, the levels of adenosine were reduced significantly compared to the wild type. When examining the level of Ca2+ influx of Raji compared to the HPRT Raji knockdown cell, there was a significant decrease in calcium influx in the knockdown cells when compared to the wild type cells. This demonstrates that HPRT had a significant impact on overall cell activation and the ability of the cells to properly influx calcium needed for their activation.

Conclusions

We conclude that purine levels significantly reduce immune cell activation in cancer and the upregulation of HPRT in malignant tissue is a contributing factors to the immunosuppressive microenvironment.

中文翻译：

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次黄嘌呤鸟嘌呤磷酸核糖基转移酶的表达通过其对嘌呤合成的调节与免疫活性呈负相关。

介绍

本研究的目的是检查升高的次黄嘌呤鸟嘌呤磷酸核糖基转移酶 (HPRT) 对肿瘤微环境中免疫反应的影响。

方法

在癌症患者中评估 HPRT 表达，并与细胞因子表达、存活率和免疫细胞浸润相关。创建 HPRT 敲低细胞系以评估 HPRT 对嘌呤表达的影响，随后对免疫细胞进行嘌呤处理以确定它们对细胞活化的影响。

结果

HPRT 表达与促炎和抗炎细胞因子的一般表达呈负相关。此外，HPRT 表达也与免疫细胞亚群的浸润呈负相关：B 细胞、CD4 + T 细胞、巨噬细胞、中性粒细胞和树突细胞 (p < 0.001) 和 CD8 + T 细胞 (p < 0.01)。当 HPRT 在 Raji 细胞系中被击倒时，与野生型相比，腺苷水平显着降低。在检查与 HPRT Raji 敲低细胞相比 Raji 的 Ca2+ 流入水平时，与野生型细胞相比，敲低细胞中的钙流入显着减少。这表明 HPRT 对整体细胞活化和细胞适当流入其活化所需的钙的能力具有显着影响。

结论

我们得出结论，嘌呤水平显着降低癌症中的免疫细胞活化，恶性组织中 HPRT 的上调是免疫抑制微环境的一个促成因素。