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

Cancer cell (2020-05-30)
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
ABSTRACT

A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy. We uncover a role for non-classical monocytes in B-ALL survival, and demonstrate monocyte abundance at B-ALL diagnosis is predictive of pediatric and adult B-ALL patient survival. We show that human B-ALL blasts alter a vascularized microenvironment promoting monocytic differentiation, while depleting leukemia-associated monocytes in B-ALL animal models prolongs disease remission in vivo. Our profiling of the B-ALL immune microenvironment identifies extrinsic regulators of B-ALL survival supporting new immune-based therapeutic approaches for high-risk B-ALL treatment.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Trichloro(1H,1H,2H,2H-perfluorooctyl)silane, 97%
Sigma-Aldrich
Fibrinogen from bovine plasma, Type I-S, 65-85% protein (≥75% of protein is clottable)
Sigma-Aldrich
Gelatin from porcine skin, gel strength 300, Type A