Drug-induced PD-L1 expression and cell stress response in breast cancer cells can be balanced by drug combination

被引:52
作者
Gilad, Yosi [1 ]
Eliaz, Yossi [2 ]
Yu, Yang [1 ]
Han, Sang Jun [1 ]
O'Malley, Bert W. [1 ]
Lonard, David M. [1 ]
机构
[1] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
关键词
FOLLOW-UP; CHEMOTHERAPY; DEATH; TUMOR; RESISTANCE; INHIBITORS; TOLERANCE; BLOCKADE; IMMUNITY; THERAPY;
D O I
10.1038/s41598-019-51537-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The impact of chemotherapy on tumor-immune system interaction can be either beneficial or harmful, which is represented by the immunogenic cell death (ICD) paradigm or overexpression of the immunosuppressive protein - programmed death ligand 1 (PD-L1). In this study we explore the impact of steroid receptor coactivator inhibitor, other targeted anti-cancer compounds and traditional chemotherapeutic agents on the expression of PD-L1 in four breast cancer (BC) cell lines. Our results show that these agents induce PD-L1 expression, yet the magnitude of this induction varies substantially across the different compounds. In addition, we utilized the E0771 ER + BC cells as a model to examine in greater detail the relationship between pharmacological pressure, cell stress and the induction of PD-L1. Our results imply that drug induced PD-L1 expression occurs in the broader context of cell-stress, without conferring acquired drug-resistance. Furthermore, a balance between BC cytotoxicity, induction of cell-stress and the overexpression of PD-L1 can be achieved through the selection of appropriate combinations of anti-cancer compounds. Therefore, we propose that drug combination can be employed not only for increasing the direct kill of cancer cells, but also as a strategy to minimize the activation of immunosuppressive and cancer cell pro-survival program responses during drug treatment.
引用
收藏
页数:8
相关论文
共 49 条
[1]   Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study [J].
Ali, H. Raza ;
Chlon, Leon ;
Pharoah, Paul D. P. ;
Markowetz, Florian ;
Caldas, Carlos .
PLOS MEDICINE, 2016, 13 (12)
[2]   Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers [J].
Avril, T. ;
Vauleron, E. ;
Chevet, E. .
ONCOGENESIS, 2017, 6 :e373-e373
[3]   Understanding the tumor immune microenvironment (TIME) for effective therapy [J].
Binnewies, Mikhail ;
Roberts, Edward W. ;
Kersten, Kelly ;
Chan, Vincent ;
Fearon, Douglas F. ;
Merad, Miriam ;
Coussens, Lisa M. ;
Gabrilovich, Dmitry I. ;
Ostrand-Rosenberg, Suzanne ;
Hedrick, Catherine C. ;
Vonderheide, Robert H. ;
Pittet, Mikael J. ;
Jain, Rakesh K. ;
Zou, Weiping ;
Howcroft, T. Kevin ;
Woodhouse, Elisa C. ;
Weinberg, Robert A. ;
Krummel, Matthew F. .
NATURE MEDICINE, 2018, 24 (05) :541-550
[4]   Activation of the PD-1/PD-L1 immune checkpoint confers tumor cell chemoresistance associated with increased metastasis [J].
Black, Madison ;
Barsoum, Ivraym B. ;
Truesdell, Peter ;
Cotechini, Tiziana ;
Macdonald-Goodfellow, Shannyn K. ;
Petroff, Margaret ;
Siemens, D. Robert ;
Koti, Madhuri ;
Craig, Andrew W. B. ;
Graham, Charles H. .
ONCOTARGET, 2016, 7 (09) :10557-10567
[5]   Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway [J].
Boussiotis, Vassiliki A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (18) :1767-1778
[6]   Targeting T Cell Co-receptors for Cancer Therapy [J].
Callahan, Margaret K. ;
Postow, Michael A. ;
Wolchok, Jedd D. .
IMMUNITY, 2016, 44 (05) :1069-1078
[7]   Regulation of PD-L1: a novel role of pro-survival signalling in cancer [J].
Chen, J. ;
Jiang, C. C. ;
Jin, L. ;
Zhang, X. D. .
ANNALS OF ONCOLOGY, 2016, 27 (03) :409-416
[8]   Endoplasmic Reticulum Stress-Activated Cell Reprogramming in Oncogenesis [J].
Chevet, Eric ;
Hetz, Claudio ;
Samali, Afshin .
CANCER DISCOVERY, 2015, 5 (06) :586-597
[9]   Tumor-Intrinsic PD-L1 Signals Regulate Cell Growth, Pathogenesis, and Autophagy in Ovarian Cancer and Melanoma [J].
Clark, Curtis A. ;
Gupta, Harshita B. ;
Sareddy, Gangadhara ;
Pandeswara, Srilakshmi ;
Lao, Shunhua ;
Yuan, Bin ;
Drerup, Justin M. ;
Padron, Alvaro ;
Conejo-Garcia, Jose ;
Murthy, Kruthi ;
Liu, Yang ;
Turk, Mary Jo ;
Thedieck, Kathrin ;
Hurez, Vincent ;
Li, Rong ;
Vadlamudi, Ratna ;
Curiel, Tyler J. .
CANCER RESEARCH, 2016, 76 (23) :6964-6974
[10]   Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment: Beyond Immune Evasion [J].
Dong, Peixin ;
Xiong, Ying ;
Yue, Junming ;
Hanley, Sharon J. B. ;
Watari, Hidemichi .
FRONTIERS IN ONCOLOGY, 2018, 8