Regulation of Programmed Death Ligand 1 (PD-L1) Expression in Breast Cancer Cell Lines In Vitro and in Immunodeficient and Humanized Tumor Mice

被引:52
作者
Rom-Jurek, Eva-Maria [1 ]
Kirchhammer, Nicole [1 ,2 ]
Ugocsai, Peter [1 ]
Ortmann, Olaf [1 ]
Wege, Anja K. [1 ]
Brockhoff, Gero [1 ]
机构
[1] Univ Med Ctr Regensburg, Dept Gynecol & Obstet, Landshuter Str 65, D-93053 Regensburg, Germany
[2] Univ Hosp Basel, Dept Biomed, Hebelstr, CH-204031 Basel, Switzerland
关键词
breast cancer cell lines; PD-(L)1; humanized tumor mice; Epirubicin; Paclitaxel; INFILTRATING LYMPHOCYTES; RECEPTOR; INHIBITORS; GROWTH;
D O I
10.3390/ijms19020563
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Programmed death ligand 1 (PD-L1) expression is an efficient strategy of tumor cells to escape immunological eradiation. However, only little is known about the factors that affect the cellular expression levels. Here we assessed the PD-L1 expression on different breast cancer cell lines under standard in vitro culture conditions and as a function of Epirubicin or Paclitaxel treatment. Moreover, we evaluated the expression in immunodeficient tumor mice as well as in humanized tumor mice (i.e., in the presence of a human immune system). We found highest PD-L1 levels in JIMT-1 and MDA-MB-231 cells. Epirubicin treatment caused a decrease and Paclitaxel treatment an increased PD-L1 expression in MDA-MB-231 cells. In addition, we identified nuclear PD-L1 in MDA-MB-231 cells. All in vivo transplanted breast cancer cell lines downregulated PD-L1 expression compared to their in vitro counterpart. Neither the gene copy number nor the presence of human immune system in humanized tumor mice had an effect on the PD-L1 content. We demonstrate that the degree of PD-L1 expression amongst breast cancer cell lines varies considerably. In addition, cytotoxic treatments and other extrinsic parameters differentially affect the expression. Hence, further investigations including in vivo evaluations are necessary to understand PD-L1 regulation for advanced breast cancer stratification.
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页数:13
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