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. 2020 May 27;8:18. doi: 10.1186/s40364-020-00197-1

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — The mechanism of CD19+ relapse in BM microenvironment. a Main interaction between negative regulatory cells, tumor cells and immune effector cells in BM microenvironment. Tregs, MDSCs and TAMs suppress CTLs, DCs, NK cells and T cells by cytokines, enzymes and cell-cell interactions. Negative regulatory cells and tumor cells attract and improve each other’s recruitment, differentiation and expansion. Tregs: regulatory T cells; MDSCs: myeloid-derived suppressor cells; TAMs: tumor associated macrophages; IDO: indoleamine-2, 3-dioxygenase; CTLs: cytotoxic T cells; DCs: dendritic cells; NK cells: natural kill cells; TGF-β: transforming growth factor β. b The negative regulation checkpoint in BM microenvironment. The PD-1/PD-L1 pathway between tumor cells and MDSCs, T cells, TAMs inhibits the proliferating of T cells and transforms T cells into induces Tregs or induces apoptosis. The CTLA-4/B7 pathway suppresses APCs while activates Tregs. (Tregs: regulatory T cells; iTregs: induced Tregs; TAMs: tumor associated macrophages; APCs: antigen-presenting cells; MDSCs: myeloid-derived suppressor cells; PD-1: programmed death-1; PD-L: programmed cell death 1 ligand)