创新背景

免疫抑制机制帮助慢性炎症阻断并减少损伤。有研究表明，内质网的压力也许可以增强免疫细胞的抑制表型，然而，支持这一过程进行的分子机制以及其如何运作与免疫细胞的联系，目前研究人员尚不清楚。

创新过程

凯斯西储大学医学院等机构的研究员在国际杂志Nature Immunology上发表研究报告《PERK 是巨噬细胞免疫抑制功能的关键代谢中心》（PERK is a critical metabolic hub for immunosuppressive function in macrophages），表示通过操控名为巨噬细胞的免疫细胞将可能成功抑制实验模型机体中实体瘤的生长。

从事医学者从未停止过与癌症的竞争。论文提出的研究将是一种帮助科学家和医学研究者开发治疗肿瘤的新方法。机体的免疫功能一般主要是由白细胞提供。巨噬细胞是白细胞的一种，对病原体的攻击起着重要作用，会通过吞噬入侵的细胞来破坏病原体，是机体免疫系统的“先锋官”。但是，即使巨噬细胞的保护作用强大，仍然会受到肿瘤细胞影响促进肿瘤生长。

研究者表示，造成癌症的实体瘤一直是人类科学难关，通过操控巨噬细胞抑制肿瘤生长研究的意义重大。据美国国家癌症研究所数据显示，包括乳腺癌、肺癌、前列腺癌和结直肠癌在内的很多实体瘤几乎占到了美国所有新发癌症病例的一半。通过这项研究，研究人员发现，改变巨噬细胞的代谢重组，会联系影响另一白细胞——T细胞，它们之间的之间的相互关联或能抑制肿瘤的生长。

随着肿瘤生长以及巨噬细胞与肿瘤细胞相互作用，将会产生一种反应性蛋白（PERK蛋白）。研究人员将其与肿瘤的生长联系起来，认为通过靶向作用巨噬细胞以及PERK蛋白或许有望阻断肿瘤的生长。敲除PERK或能抑制肿瘤巨噬细胞中的下游代谢信号，从而促进更多T细胞抵御癌细胞。研究结果表明，PERK蛋白主要参与了巨噬细胞中多项关键通路，当编码该蛋白基因移除后，巨噬细胞通路被阻断，或许就无法促进肿瘤的生长，造成肿瘤萎缩。

后续进一步实验结果表明，将PERK抑制剂药物与抗PD-1抑制剂组合后或许就能明显抑制肿瘤的生长，研究人员希望能够识别出一种特殊的临床药物来扮演PERK蛋白质的抑制剂。

创新关键点

通过PERK蛋白改组阻断巨噬细胞路径，帮助阻断实体瘤生长路径。

PERK blocking macrophage pathway promises to stop tumor growth

Researchers from Case Western Reserve University School of Medicine and other institutions published a research report in the international journal Nature Immunology "PERK is a Key Metabolic Center for Macrophage Immunosuppressive Function".It is possible to successfully suppress the growth of solid tumors in experimental models by manipulating immune cells called macrophages.
Medical practitioners have never stopped competing with cancer. The research presented in the paper will be a way to help scientists and medical researchers develop new ways to treat tumors. The immune function of the body is generally mainly provided by white blood cells. Macrophages are a type of white blood cells that play an important role in the attack of pathogens. They destroy pathogens by phagocytosing invading cells. They are the "pioneer" of the body's immune system. However, even if the protective effect of macrophages is strong, they can still be influenced by tumor cells to promote tumor growth.
The researchers said that solid tumors that cause cancer have always been a problem for human science, and the study of inhibiting tumor growth by manipulating macrophages is of great significance. Many solid tumors, including breast, lung, prostate and colorectal cancers, account for nearly half of all new cancer cases in the United States, according to the National Cancer Institute. Through this study, the researchers found that altering the metabolic reorganization of macrophages can affect another white blood cell, T cells, and that their interconnectedness may inhibit tumor growth.
As tumors grow and macrophages interact with tumor cells, a reactive protein (PERK protein) is produced. The researchers linked it to tumor growth, suggesting that targeting macrophages and the PERK protein might be expected to block tumor growth. Knockout of PERK may inhibit downstream metabolic signaling in tumor macrophages, thereby promoting more T cells to fight cancer cells. The research results show that PERK protein is mainly involved in a number of key pathways in macrophages. When the gene encoding this protein is removed, the macrophage pathway is blocked, which may not promote tumor growth and cause tumor shrinkage.
The results of follow-up further experiments showed that combining PERK inhibitor drugs with anti-PD-1 inhibitors may significantly inhibit tumor growth. The researchers hope to identify a specific clinical drug that acts as an inhibitor of PERK protein.