Immune checkpoint regulator PD-L1 expression on tumor cells by contacting CD11b positive bone marrow derived stromal cells

Cell Communication and Signaling

Research

Xiaohong Wang¹  Shulin Li²  Xueqing Xia²  Jiemiao Hu²  Hyangsoon Noh²  Arun Satelli² 

[1] Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA;Department of Pediatrics–Research, The University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA;

关键词: Immune checkpoint PD-L1;    Bone marrow derived cells;    Tumor microenvironment;    CD11b;    Chemotherapy resistance;   

DOI  :  10.1186/s12964-015-0093-y

 received in 2014-10-16, accepted in 2015-02-12,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundExpression of programmed cell death ligand 1 (PD-L1) is an important process by which tumor cells suppress antitumor immunity in the tumor microenvironment. Bone marrow (BM)–derived immune cells are an important component of the tumor microenvironment. However, the link between PD-L1 induction on tumor cells and communication with BM cells is unknown.ResultsThis study demonstrates that BM cells have a direct effect in inducing PD-L1 expression on tumor cells, which contributes to the tumor cells’ drug resistance. This novel discovery was revealed using a co-incubation system with BM cells and tumor cells. BM cells from wild-type C57BL6 mice and the immune-deficient mouse strains B-cell−/−, CD28−/−, perforin−/−, and Rag2−/− but not CD11b−/− dramatically increased the expression of tumor cell surface PD-L1. This PD-L1 induction was dependent on CD11b-positive BM cells through direct contact with tumor cells. Furthermore, p38 signaling was activated in tumor cells after co-incubation with BM cells, whereas the expression of PD-L1 was remarkably decreased after co-culture of cells treated with a p38 inhibitor. The increase in PD-L1 induced by BM cell co-culture protected tumor cells from drug-induced apoptosis.ConclusionsPD-L1 expression is increased on tumor cells by direct contact with BM-derived CD11b-positive cells through the p38 signaling pathway. PD-L1 may play an important role in drug resistance, which often causes failure of the antitumor response.

【 授权许可】

Unknown   
© Noh et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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.