小柯机器人

美国国立卫生研究院Rosandra N. Kaplan小组发现，基因工程化的髓细胞能够重新平衡转移过程中的核心免疫抑制程序。这一研究成果于2021年3月24日在线发表在国际学术期刊《细胞》上。

研究人员确定了主要由髓样细胞表达的转移前微环境形成中的核心免疫抑制基因特征。研究人员通过利用基因工程髓样细胞（GEMy）提供IL-12来调节转移性微环境，从而针对这种免疫抑制程序。数据表明，IL12-GEMy治疗可通过激活抗原呈递和T细胞活化来逆转转移前微环境中的免疫抑制，从而减少转移性和原发性肿瘤负担，并提高荷瘤小鼠的存活率。

研究人员证明，IL12-GEMy可以功能性地调节转移前微环境中免疫抑制的核心程序，从而成功地重新平衡癌症中转移微环境失调。

据悉，转移是与癌症相关的死亡的主要原因，因此，了解转移微环境对于有效地靶向该过程是必要的。在临床上可检测到的转移性疾病发生之前，微环境变化发生在远处。然而，转移过程中关键的微环境调节信号仍不明确。

附：英文原文

Title: Genetically engineered myeloid cells rebalance the core immune suppression program in metastasis

Author: Sabina Kaczanowska, Daniel W. Beury, Vishaka Gopalan, Arielle K. Tycko, Haiying Qin, Miranda E. Clements, Justin Drake, Chiadika Nwanze, Meera Murgai, Zachary Rae, Wei Ju, Katherine A. Alexander, Jessica Kline, Cristina F. Contreras, Kristin M. Wessel, Shil Patel, Sridhar Hannenhalli, Michael C. Kelly, Rosandra N. Kaplan

Issue&Volume: 2021-03-24

Abstract: Metastasis is the leading cause of cancer-related deaths, and greater knowledge ofthe metastatic microenvironment is necessary to effectively target this process. Microenvironmentalchanges occur at distant sites prior to clinically detectable metastatic disease;however, the key niche regulatory signals during metastatic progression remain poorlycharacterized. Here, we identify a core immune suppression gene signature in pre-metastaticniche formation that is expressed predominantly by myeloid cells. We target this immunesuppression program by utilizing genetically engineered myeloid cells (GEMys) to deliverIL-12 to modulate the metastatic microenvironment. Our data demonstrate that IL12-GEMytreatment reverses immune suppression in the pre-metastatic niche by activating antigenpresentation and T cell activation, resulting in reduced metastatic and primary tumorburden and improved survival of tumor-bearing mice. We demonstrate that IL12-GEMyscan functionally modulate the core program of immune suppression in the pre-metastaticniche to successfully rebalance the dysregulated metastatic microenvironment in cancer.

DOI: 10.1016/j.cell.2021.02.048

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00237-3