纽约大学医学院Iannis Aifantis、 William L. Carroll和Matthew T. Witkowski研究组合作取得一项新突破。他们发现B细胞急性淋巴细胞白血病（B-ALL）中免疫微环境存在广泛重塑。相关论文在线发表在2020年5月28日出版的《癌细胞》杂志上。

利用单细胞方法，研究人员证明在疾病发生和常规化疗后复发过程中，B-ALL骨髓免疫微环境发生重塑。研究人员发现非经典单核细胞在B-ALL生存中的功能，并证明在B-ALL诊断中单核细胞的丰度可预测小儿和成人B-ALL患者的生存期。

研究显示，人B-ALL原始细胞的改变促进了单核细胞分化的血管化微环境；而在B-ALL动物模型中，白血病相关单核细胞的耗竭则延长了体内疾病的缓解时间。 研究人员对B-ALL免疫微环境的分析确定了B-ALL生存的外在调节因子，提供了针对高风险B-ALL的新的免疫疗法。

据悉，部分B-ALL患者会复发并对治疗产生的耐药性疾病缺乏抵抗力。骨髓微环境可能促进B-ALL的进展和对治疗不敏感。

附：英文原文

Title: Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia

Author: Matthew T. Witkowski, Igor Dolgalev, Nikki A. Evensen, Chao Ma, Tiffany Chambers, Kathryn G. Roberts, Sheetal Sreeram, Yuling Dai, Anastasia N. Tikhonova, Audrey Lasry, Chunxu Qu, Deqing Pei, Cheng Cheng, Gabriel A. Robbins, Joanna Pierro, Shanmugapriya Selvaraj, Valeria Mezzano, Marla Daves, Philip J. Lupo, Michael E. Scheurer, Cynthia A. Loomis, Charles G. Mullighan, Weiqiang Chen, Karen R. Rabin, Aristotelis Tsirigos, William L. Carroll, Iannis Aifantis

Issue&Volume: 2020-05-28

Abstract: A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse andsuccumb to therapy-resistant disease. The bone marrow microenvironment may supportB-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrateB-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequentre-emergence during conventional chemotherapy. We uncover a role for non-classicalmonocytes in B-ALL survival, and demonstrate monocyte abundance at B-ALL diagnosisis predictive of pediatric and adult B-ALL patient survival. We show that human B-ALLblasts alter a vascularized microenvironment promoting monocytic differentiation,while depleting leukemia-associated monocytes in B-ALL animal models prolongs diseaseremission in vivo. Our profiling of the B-ALL immune microenvironment identifies extrinsic regulatorsof B-ALL survival supporting new immune-based therapeutic approaches for high-riskB-ALL treatment.

DOI: 10.1016/j.ccell.2020.04.015

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30214-2