小柯机器人

美国哈佛医学院Peter V. Kharchenko、Ninib Baryawno等研究人员合作发现，人类前列腺癌骨转移具有一个可治疗靶向的免疫抑制微环境。相关论文于2021年10月15日在线发表于国际学术期刊《癌细胞》上。

研究人员试图通过分析来自骨转移性前列腺肿瘤、有转移灶的骨髓、无转移灶的骨髓以及来自无癌、骨科病人和健康人的骨髓单细胞，来定义骨髓（BM）微环境的不同特征。转移性前列腺癌（PCa）与多方面的免疫改变有关，特别是不同T细胞亚群的衰竭，以及巨噬细胞的出现与PCa骨转移的特定状态有关。趋化因子CCL20在骨髓细胞中明显高表达，其在T细胞上的同源CCR6受体也是如此。破坏小鼠的CCL20-CCR6轴使T细胞的反应性得到恢复，并大大延长了动物的生存期。对PCa骨转移的比较性高分辨率分析表明，有针对性地解除局部免疫抑制能够达到治疗效果。

据悉，骨转移是癌症的破坏性并发症。它们在PCa中特别常见，代表着不治之症，并且对免疫疗法具有抗药性。

附：英文原文

Title: Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment

Author: Youmna Kfoury, Ninib Baryawno, Nicolas Severe, Shenglin Mei, Karin Gustafsson, Taghreed Hirz, Thomas Brouse, Elizabeth W. Scadden, Anna A. Igolkina, Konstantinos Kokkaliaris, Bryan D. Choi, Nikolas Barkas, Mark A. Randolph, John H. Shin, Philip J. Saylor, David T. Scadden, David B. Sykes, Peter V. Kharchenko

Issue&Volume: 2021-10-15

Abstract: Bone metastases are devastating complications of cancer. They are particularly commonin prostate cancer (PCa), represent incurable disease, and are refractory to immunotherapy.We seek to define distinct features of the bone marrow (BM) microenvironment by analyzingsingle cells from bone metastatic prostate tumors, involved BM, uninvolved BM, andBM from cancer-free, orthopedic patients, and healthy individuals. Metastatic PCais associated with multifaceted immune distortion, specifically exhaustion of distinctT cell subsets, appearance of macrophages with states specific to PCa bone metastases.The chemokine CCL20 is notably overexpressed by myeloid cells, as is its cognate CCR6receptor on T cells. Disruption of the CCL20-CCR6 axis in mice with syngeneic PCabone metastases restores T cell reactivity and significantly prolongs animal survival.Comparative high-resolution analysis of PCa bone metastases shows a targeted approachfor relieving local immunosuppression for therapeutic effect.

DOI: 10.1016/j.ccell.2021.09.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00494-3

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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