美国德克萨斯大学MD安德森癌症中心Filippo G. Giancotti课题组在研究中取得进展。他们的最新发现揭示了Polycomb抑制复合物1通过协调细胞干性和免疫抑制来驱动双阴性前列腺癌转移。相关论文发表在2019年8月12日出版的《癌细胞》杂志上。

研究人员发现，Polycomb抑制复合物1（PRC1）驱动双阴性前列腺癌（DNPC）在骨骼和内脏器官的定植。体内遗传筛选将CCL2鉴定为PRC1诱导的主要促转移基因。CCL2调控细胞自我更新并诱导M2样肿瘤相关巨噬细胞和调节性T细胞的募集，从而协调转移起始与免疫抑制以及新血管生成。PRC1的催化抑制剂与免疫检查点疗法协作以逆转这些过程并抑制DNPC在转基因小鼠移植模型中的转移。这些结果揭示PRC1协调细胞干性与免疫逃避以及促进新血管生成，并指出在DNPC中靶向PRC1的潜在临床效用。

据介绍，转移部位肿瘤免疫逃避的机制尚不清楚。
 

附：英文原文

Title: The Polycomb Repressor Complex 1 Drives Double-Negative Prostate Cancer Metastasis by Coordinating Stemness and Immune Suppression

Author: Wenjing Su, Hyun Ho Han, Yan Wang, Boyu Zhang, Bing Zhou, Yuanming Cheng, Alekya Rumandla, Sreeharsha Gurrapu, Goutam Chakraborty, Jie Su, Guangli Yang, Xin Liang, Guocan Wang, Neal Rosen, Howard I. Scher, Ouathek Ouerfelli, Filippo G. Giancotti

Issue&Volume: Volume 36 Issue 2

Abstract: The mechanisms that enable immune evasion at metastatic sites are poorly understood. We show that the Polycomb Repressor Complex 1 (PRC1) drives colonization of the bones and visceral organs in double-negative prostate cancer (DNPC). In vivo genetic screening identifies CCL2 as the top prometastatic gene induced by PRC1. CCL2 governs self-renewal and induces the recruitment of M2-like tumor-associated macrophages and regulatory T cells, thus coordinating metastasis initiation with immune suppression and neoangiogenesis. A catalytic inhibitor of PRC1 cooperates with immune checkpoint therapy to reverse these processes and suppress metastasis in genetically engineered mouse transplantation models of DNPC. These results reveal that PRC1 coordinates stemness with immune evasion and neoangiogenesis and point to the potential clinical utility of targeting PRC1 in DNPC.

DOI: https://doi.org/10.1016/j.ccell.2019.06.009

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30300-9